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Background: Lutetium-177 [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 improves survival and quality of life in patients with metastatic castration-resistant prostate cancer, but whether it confers a benefit in hormone-sensitive disease is unknown. We aimed to evaluate [ 177 Lu]Lu-PSMA-617 before docetaxel treatment in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer., Methods: UpFrontPSMA was an investigator-initiated, multicentre, open-label, randomised, phase 2 trial done at 11 Australian hospitals. Eligible patients had prostate adenocarcinoma without clinically significant neuroendocrine differentiation or small-cell histology, were aged 18 years or older, had less than 4 weeks on androgen deprivation therapy, had an Eastern Cooperative Oncology Group performance status of 0-2, and had high-volume PSMA-avid disease on [ 68 Ga]Ga-PSMA-11 PET-CT with no major discordance on 2-[ 18 F] fluorodeoxyglucose-PET-CT. Patients were randomly assigned (1:1) to the experimental treatment ([ 177 Lu]Lu-PSMA-617 followed 6 weeks later by docetaxel) or standard-of-care treatment (docetaxel alone) using computer-based block randomisation with random block sizes, stratified by disease volume by conventional imaging and duration of androgen deprivation therapy at the time of registration. Neither patients nor investigators were masked to treatment assignment. Patients in the experimental group received two cycles of [ 177 Lu]Lu-PSMA-617 7·5 GBq every 6 weeks intravenously, followed 6 weeks later by six cycles of docetaxel 75 mg/m 2 every 3 weeks intravenously, whereas patients in the standard-of-care treatment group received six cycles of docetaxel 75 mg/m 2 every 3 weeks intravenously. All patients received continuous androgen deprivation therapy. The primary endpoint was undetectable prostate-specific antigen (≤0·2 ng/mL) at 48 weeks, assessed using a modified intention-to-treat analysis. The trial is registered with ClinicalTrials.gov, NCT04343885., Findings: Between May 5, 2020, and April 18, 2023, 130 patients were randomly assigned, 63 (48%) to [ 177 Lu]Lu-PSMA-617 plus docetaxel and 67 (52%) to docetaxel alone. All patients were male and no race or ethnicity data were collected. Median follow-up was 2·5 years (IQR 1·8-3·0). Four patients in the docetaxel alone group withdrew consent after randomisation and no data beyond screening were collected. An additional four patients were not evaluable for the primary endpoint at 48 weeks (two in each group). 25 (41%) of 61 patients (95% CI 30-54) in the [ 177 Lu]Lu-PSMA-617 plus docetaxel group had undetectable PSA at 48 weeks compared with ten (16%) of 61 patients (9-28) in the docetaxel alone group (OR 3·88, 95% CI 1·61-9·38; p=0·0020). The most common grade 3 or 4 treatment-related adverse events were febrile neutropenia (seven [11%] of 63 patients in the [ 177 Lu]Lu-PSMA-617 plus docetaxel group vs six [10%] of 63 patients in the docetaxel alone group) and diarrhoea (four [6%] of 63 patients vs none). Serious adverse events occurred in 16 (25%) patients in the [ 177 Lu]Lu-PSMA-617 plus docetaxel group (none were definitely related to [ 177 Lu]Lu-PSMA-617) and 16 (25%) patients in the docetaxel alone group. No treatment-related deaths occurred., Interpretation: [ 177 Lu]Lu-PSMA-617 followed by docetaxel improved antitumour activity in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer compared with docetaxel alone, without increased toxic effects. Our data potentially support a role for [ 177 Lu]Lu-PSMA-617 in metastatic hormone-sensitive prostate cancer., Funding: Prostate Cancer Research Alliance (Movember Foundation and Australian Government Medical Research Future Fund), US Department of Defence Impact Award-Clinical Trials, Endocyte/Advanced Accelerator Applications (a Novartis company), Australian Nuclear Science and Technology Organization, Victorian Cancer Agency, University of Melbourne, and Peter MacCallum Cancer Foundation., Competing Interests: Declaration of interests AAA reports grants from Aptevo Therapeutics (institutional), Astellas (investigator), Astellas (institutional), AstraZeneca (institutional), AstraZeneca (investigator), Bionomics (institutional), Bristol Myers Squibb (institutional), Eli Lilly (institutional), Exelixis (institutional), Gilead Sciences (institutional), GlaxoSmithKline (institutional), Hinova (institutional), Ipsen (institutional), Janssen (institutional), MedImmune (institutional), Merck Serono (investigator), Merck Serono (institutional), Merck Sharpe & Dohme (institutional), Novartis (institutional), Pfizer (institutional), Sanofi Aventis (institutional), and SYNthorx (institutional); consulting fees from Astellas, Novartis, Janssen, Sanofi, AstraZeneca, Bristol Myers Squibb, Tolmar, Telix Pharma, Merck, Bayer, Ipsen, Merck Serono, Amgen, and Noxopharm; honoraria from Janssen, Astellas, Novartis, Tolmar, Amgen, Pfizer, Bayer, Telix Pharma, Bristol Myers Squibb, Merck Serono, AstraZeneca, Sanofi, Ipsen, Merck Sharp & Dohme, Noxopharm, Daiichi Sankyo, and Arvinas; speakers' bureau fees from Astellas, Novartis, Amgen, Bayer, Janssen, Ipsen, Bristol Myers Squibb, and Merck Serono; support for attending meetings from Amgen, Astellas, Bayer, Hinova, Janssen, Merck Serono, Novartis, Pfizer, and Tolmar; participation on data safety monitoring or advisory boards for Arvinas, Astellas, Novartis, Janssen, Sanofi, AstraZeneca, Bristol Myers Squibb, Tolmar, Telix Pharma, Merck Sharpe & Dohme, Bayer, Ipsen, Merck Serono, Amgen, Noxopharm, and Daiichi Sankyo. MV reports personal fees from AstraZeneca and Merck Sharpe & Dohme and grants (to their institution) from AstraZeneca, Merck Sharpe & Dohme, Alpine Immune Sciences, Virocure, Hinova, Atridia/Hengrui, Antengene, and Biogene. AJW declares grants to their institution from Merck Sharpe & Dohme; consulting fees from Merck Sharpe & Dohme, Bayer, Bristol Myers Squibb, Pfizer, Ipsen, and Astellas; honoraria from Astellas and Bristol Myers Squibb; and support for attending meetings from Bayer. AG reports grants from Sun Pharma; consulting fees from Regeneron and Bayer; support to attend meetings from Sun Pharma and Bristol Myers Squibb; and participation in a data safety monitoring or advisory board for Regeneron and Bayer. RJF reports committee involvement in the Australasian Radiopharmaceutical Trials Network (unpaid). LE reports research grant support (to their institution) from Novartis and Clarity Pharma; consulting fees for lectures or advisory boards from Astellas, Janssen, AstraZeneca, Clarity, Novartis, and Telix in the past 5 years; and philanthropic grant support from the Prostate Cancer Foundation, St Vincent's Clinic Research Foundation, and the Curran Foundation. DGM has received reimbursement for advisory board or speaker bureau activity from the following companies (in the past 36 months): Janssen, Astellas, Bayer, AstraZeneca, Mundipharma, Novartis, and Ipsen. AR has received reimbursement for advisory board or speaker bureau activity from the following companies: AstraZeneca, Daiichi Sankyo, Lily, Pfizer, Merck Sharpe & Dohme, Roche, and Novartis. DAP reports personal fees from Eisai. MSH reports grants and receipt of equipment, materials, drugs, medical writing, gifts, or other services from the Prostate Cancer Foundation, NHRMC, Movember, US Department of Defense, Medical Research Future Fund, Bayer, Peter MacCallum Foundation, Isotopia, and the Australian Nuclear Science and Technology Organisation; consulting fees from Merck Sharp & Dohme and Novartis; honoraria from Janssen, Novartis, and AstraZeneca; and support for meetings from Merck Sharp & Dohme, Novartis, Janssen, AstraZeneca, and Astellas. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [ 68 Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection., Objective: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites., Design, Setting, and Participants: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162., Intervention: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation., Outcome Measurements and Statistical Analysis: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis., Conclusions: Patient enrolment began in March 2022, with recruitment expected to take 36 mo., Patient Summary: For patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Enzalutamide and lutetium-177 [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [ 177 Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer., Methods: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [ 68 Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [ 177 Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing., Findings: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [ 177 Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [ 177 Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [ 177 Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [ 177 Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [ 177 Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [ 177 Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group., Interpretation: The addition of [ 177 Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer., Funding: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company)., Competing Interests: Declaration of interests LE reports research grant support (to their institution) from Novartis and Clarity Pharma; consulting fees for lectures or advisory boards from Astellas, Janssen, AstraZeneca, Clarity, Novartis, and Telix in the past 5 years; and philanthropic grant support from the Prostate Cancer Foundation, St Vincent's Clinic Research Foundation, and Curran Foundation. SSa reports grants from Novartis/AAA, AstraZeneca, Merck Sharp & Dohme, Genentech, Pfizer, Amgen, and Senhwa to their institution; and personal fees from AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb, and AstraZeneca to their institution, outside the submitted work. CG donated personal fees from Astellas, Janssen, AstraZeneca, Bristol Myers Squibb, Pfizer/EMD Serono, Ipsen, Astellas, and MSD, direct and complete, to a third party not-for-profit. CG declares consulting fees (unrelated to this work) from Novotech, Cadex Geonomics, and BCAL Diagnostics; and participation on an advisory board for Alloplex. MSH reports grants and receipt of equipment, materials, drugs, medical writing, gifts, or other services from the Prostate Cancer Foundation, National Health and Medical Research Council (NHRMC), Movember, US Department of Defense, Medical Research Future Fund, Bayer, Peter MacCallum Foundation, Isotopia, and the Australian Nuclear Science and Technology Organisation; consulting fees from Merck Sharp & Dohme and Novartis; honoraria from Janssen, Novartis, AstraZeneca, and Astellas; support for meetings from Merck Sharp & Dohme, Novartis, Janssen, AstraZeneca, and Astellas; leadership or fiduciary role in other board from Australian Friends of Sheba; and other financial or non-financial interests from Peter MacCallum Cancer Centre and the University of Melbourne. DAP reports personal fees from Ipsen and Eisai, all outside the submitted work. RJF reports institution funding and consulting fees from AIQ Solutions, outside the submitted work; and committee involvement in the Australasian Radiopharmaceutical Trials Network (unpaid). MRS reports grants to his institution from the Australian NHMRC, Cancer Australia, Astellas, Amgen, AstraZeneca, Bayer, Bionomics, Bristol Myers Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, and Tilray, all outside the submitted work. IDD reports grants from the NHMRC, during the conduct of the study; and institutional payments to support prostate cancer trials from Pfizer, ANZUP Cancer Trials Group, Bayer, Astellas, Janssen, Movember Foundation, and Merck Sharp & Dohme, outside the submitted work. IDD is unremunerated Chair of the ANZUP Cancer Trials Group and is supported in part by an Australian NHMRC Investigator Grant (grant number 2016274). AMJ reports consulting or advisory roles (to their institution) from Janssen Oncology, Pfizer, and Astellas Pharma; and research funding (to their institution) from Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genentech, Bayer, Lilly, Pfizer, and AstraZeneca. AW declares consulting fees from MSD, Eisai, Bristol Myers Squibb, and Astellas; honoraria from Eisai and MSD; and participation on an advisory board from Loxo-Lilly, MSD, and Astellas. DP declares support for travel from Astellas and participation on an advisory board from Astellas. MC reports advisory board fees from Astellas. MV reports personal fees from AstraZeneca and MSD. AYZ reports grants or contracts from Astellas, Amgen, AstraZeneca, Bionomics, Bristol Myers Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, and Tilray; consulting fees from Merck Sharpe & Dohme; honoraria from Merck Sharpe & Dohme, Astellas, Bayer, Pfizer, Merck, Mundipharma, Janssen, and AstraZeneca; and participation on a data safety monitoring board or advisory board from Merck, Merck Sharpe & Dohme, Astellas, and Bayer. JCG reports consulting fees from Bristol Myers Squibb, GlaxoSmithKline, and MSD; honoraria from Bayer, Ipsen, Eisai, Janssen, GlaxoSmithKline, and MSD; support to attend meetings from Bayer and BeiGene; and participation on a data safety monitoring board or advisory board from AstraZeneca. LH reports support for the present manuscript from Astellas; research funding from Astellas, Bayer, and Imagion; participation on advisory boards from Astellas, Bayer, Janssen, and MSD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Astellas, Bayer, Janssen, and MSD; support for attending meetings from Bayer; a provisional patent (Australian number 2022902527, Prognostic Markers [plasma lipid prognostic signature in metastatic prostate cancer]; patent owned by the Chris O'Brien Lifehouse [their institution]); participation on a data safety monitoring board or advisory board from Astellas, Bayer, and Imagion; advisory board leadership role for ANZUP; and stock or stock options from Connected Medical Solutions. SY reports grants or contracts from NHMRC, Cancer Australia, Astellas, Amgen, AstraZeneca, Bionomics, Bristol Myers Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, and Tilray; and support for attending meetings from Bayer. All other authors declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Accurate primary staging of renal cancer with conventional imaging is challenging. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) may serve to improve the accuracy of renal cancer staging., Objective: To determine clinicopathological and management differences for primary renal cancer staged with PSMA PET/CT in comparison to conventional imaging., Design, Setting, and Participants: We conducted a retrospective cohort study of PSMA PET/CT scans performed for primary staging of renal cancer and incidental renal lesions at three sites in Brisbane, Australia between June 2015 and June 2020. Clinical characteristics, imaging, and histopathology were reviewed., Outcome Measurements and Statistical Analysis: Clinicopathological and management differences according to staging modality (PSMA PET/CT, conventional imaging) were assessed. Descriptive statistics were used to report demographics and clinical parameters. Nonparametric methods were used for statistical analysis. Fisher's exact test was used for comparison of small-cell size categorical variables., Results and Limitations: From a total of 120 PSMA PET/CT scans, 61 were included (52 staging, 9 incidental) for predominantly males (74%) with a mean age of 65.1 yr (standard deviation 12.0). Most primary lesions (40/51) were clear-cell renal cell carcinoma (ccRCC; 98% PSMA-avid), eight were non-ccRCC (75% PSMA-avid), and three were non-RCC (oncocytoma; 67% PSMA-avid). PSMA PET identified a greater number of presumed metastatic lesions than conventional imaging (195 vs 160). A management change was observed for 32% of patients (20% major, 12% minor). Limitations include the retrospective design and selection bias, lack of blinding to PSMA reporting, and the use of different PSMA radiotracers., Conclusions: PSMA PET/CT detected more metastases than conventional imaging and most renal cancers were PSMA-avid, resulting in a management change for one-third of the patients., Patient Summary: We looked at a newer type of scan called PSMA PET/CT for first staging of kidney cancer. We found that this detects more metastasis and helps in decisions on changes in treatment for some patients. This type of imaging is a useful addition to conventional scans in tricky cases and may help in better selection of suitable treatments, but more studies are required., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [ 177 Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]fluoro-2-deoxy-D-glucose (2-[ 18 F]FDG) PET-CT., Methods: TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[ 18 F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [ 177 Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m 2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete., Findings: 291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [ 177 Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [ 177 Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [ 177 Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [ 177 Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference -0·5 months [95% CI -3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1)., Interpretation: These results support the use of [ 177 Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[ 18 F]FDG-discordant disease., Funding: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It's a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman's Ride., Competing Interests: Declaration of interests MSH reports research grant support (to their institution) from Novartis (including AAA and Endocyte), Australian Nuclear Science and Technology Organization (ANSTO), Bayer, Isotopia, and MIM; and consulting fees for lectures or advisory boards from Astellas and AstraZeneca in the past 2 years, and from Janssen, MSD, and Mundipharma in the past 5 years. LE reports personal fees from AstraZenca, Janssen, and Astellas, outside the submitted work. SS reports grants from AAA, AstraZeneca, MSD, and Genetech to their institution; and personal fees from AstraZeneca, MSD, Bristol Myers Squibb, and AstraZeneca to their institution, outside the submitted work. DAP reports personal fees from Ipsen and Eisai, outside the submitted work. RJF reports institution funding and consulting fees from AIQ Solutions, outside of the submitted work; and committee involvement in the Australasian Radiopharmaceutical Trials Network (unpaid). CG donated personal fees from Astellas, Janssen, AstraZeneca, Bristol Myers Squibb, EMD Serono, Ipsen, Astellas, and MSD, direct and complete, to a third party not-for-profit. AMS reports trial or research funding from EMD Serono, ITM, AVID, Medimmune, Telix, Adalta, Fusion, Antengene, Earli, Curis, and Cyclotek; grants from the Australian National Health and Medical Research Council (NHMRC) and Medical Research Future Fund (MRFF), including an NHMRC Investigator Grant; and board and advisory committee involvement for the Australian and New Zealand Society of Nuclear Medicine and Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group (unpaid); all outside the submitted work. EMK reports personal fees from Astellas Pharma, Janssen, Pfizer, Ipsen, and Roche, all outside the submitted work; and is supported by a Prostate Cancer Foundation Young Investigator Award and University of British Columbia Killam Postdoctoral Fellowship. AAA reports grants or personal fees from Janssen, Astellas, Novartis, Merck Serono, Tolmar, Amgen, Pfizer, Bayer, Telix Pharmaceuticals, Bristol Myers Squibb, Sanofi, Noxopharm, AstraZeneca, Ipsen, MSD, Aculeus Therapeutics, and Daiichi Sankyo; and grants from Astellas (investigator), Merck Serono (investigator), AstraZeneca (investigator), Bristol Myers Squibb (institutional), AstraZeneca (institutional), Aptevo Therapeutics (institutional), GlaxoSmithKline (institutional), Pfizer (institutional), MedImmune (institutional), Astellas (institutional), Synthorx (institutional), Bionomics (institutional), Sanofi Aventis (institutional), Novartis (institutional), Ipsen (institutional), Exelixis (institutional), MSD (institutional), Janssen (institutional), Eli Lilly (institutional), Gilead Sciences (institutional), Merck Serono (institutional), and Hinova (institutional), all outside the submitted work. MRS reports grants to his institution from the NHMRC, Cancer Australia, Astellas, Amgen, AstraZeneca, Bayer, Bionomics, Bristol Myers Squibb, Celgene, Medivation, MSD, Pfizer, Roche, Sanofi, and Tilray, all outside the submitted work. IDD reports grants from the NHMRC, during the conduct of the study; and institutional payments to support prostate cancer trials from Pfizer, the ANZUP Cancer Trials Group, Bayer, Astellas, Janssen, Movember Foundation, and MSD, outside the submitted work. IDD is also unremunerated Chair of the ANZUP Cancer Trials Group, and is supported in part by an NHMRC Investigator Grant (grant number 2016274). AMJ reports consulting or advisory roles (to their institution) from Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, Eisai, Bayer, and Astellas Pharma; and research funding (to their institution) from Bristol Myers Squibb, Janssen Oncology, MSD, Mayne Pharma, Genentech, Bayer, Lilly, Pfizer, and AstraZeneca. AI reports personal fees for a consulting role for Curium Pharma and payment to their institution for a consulting role from Ambrx Pharma, all outside the submitted work. AJW reports a consulting role for and travel support from Bayer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cardiac metastases from neuroendocrine neoplasms (NENs) are being detected with increasing frequency, although the optimal imaging strategy remains unclear. We performed a single-center retrospective study to explore the role of somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT) and cardiac magnetic resonance imaging (CMR) in NEN cardiac metastases, determine the degree of concordance between the findings of these imaging modalities, and examine the advantages and disadvantages of each imaging technique. A secondary aim was to determine if cardiac metastases were associated with adverse cardiac events during peptide receptor radionuclide therapy (PRRT)., Methods and Results: 19 patients with NEN cardiac metastases were identified. A retrospective review of electronic medical records was performed, and if available SSTR PET/CT and CMR were blindly re-reviewed by imaging specialists, documenting the number and location of cardiac metastases. All 19 patients had SSTR PET/CT, and 10/19 patients had CMR. SSTR PET/CT identified more metastases than CMR. When identified on CMR, metastases were more accurately localized. 12/19 patients received PRRT, with no cardiac adverse effects., Conclusion: SSTR PET/CT and CMR are complementary investigations in the imaging of NEN cardiac metastases. SSTR PET/CT appears more sensitive for lesion detection, and CMR offers better lesion characterization. Both investigations present useful information for the planning of treatment including PRRT, which was administered safely., (© 2023. The Author(s).)

Purpose: There is an emerging role of the use of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in renal cell carcinoma. Herein, we report our experience in use of PSMA PET in recurrent or metastatic renal cell carcinoma (RCC)., Methods: A retrospective analysis of all patients who underwent PSMA PET for suspected recurrent or de-novo metastatic RCC between 2015 and 2020 at three institutions was performed. The primary outcome was change in management (intensification or de-intensification) following PSMA PET scan. Secondary outcomes included histopathological correlation of PSMA avid sites, comparison of sites of disease on PSMA PET to diagnostic CT and time to systemic treatment., (© 2023. The Author(s).)

Purpose: The O-(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation., Methods: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBR max ), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBR max /TBR mean ) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD])., Results: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBR max , and TBR mean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement., Conclusion: The FIG study credentialing program has increased expertise across study sites. TBR max and TBR mean were robust, with considerable variability in BTV delineation and image interpretation observed., (© 2023. The Author(s).)

Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT. Our statement has been created on the basis of clinical demand and concerns regarding the precipitation of hormonal crises. A formal literature review was conducted to identify available studies. A total of 19 Australian and New Zealand experts in the fields of medical oncology, nuclear medicine, anaesthetics, and endocrinology collaborated on this consensus statement. The main focus is on carcinoid crises. Other hormonal crises seen in patients with functional pancreatic NENs are addressed briefly. These recommendations are relevant to PRRT centres internationally and should be tailored to local experience and available resources., (© 2022 S. Karger AG, Basel.)

Background: The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18 F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18 F-FDG uptake as a surrogate marker., Methods: A retrospective audit was conducted of the brain 18 F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels., Results: The expected negative association between serum glucose levels and whole brain 18 F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain., Conclusion: In a real-world clinical PET setting, cerebral 18 F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia., (© 2022. The Author(s).)

Abstract: 99m Tc-sestamibi thyroid scintigraphy (STS) can aid in differentiating between types 1 and 2 amiodarone-induced thyrotoxicosis (AIT). We present a consecutive case series of 4 men (aged 56-75 years) in whom both 99m Tc-STS and thyroid histology were consistent with a diagnosis of type 2 AIT, representing the first reported histopathologic correlation for this diagnostic test. Median amiodarone treatment duration was 26 months (range, 10-39 months), and amiodarone was discontinued a median of 3 months preoperatively (range, 2-4 months) in all 4 cases. 99m Tc-STS is a promising functional imaging modality, which has the potential to aid clinicians in the diagnostic workup and treatment of AIT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Venous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning., Methods: Patients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality., Results: Fourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement., Conclusions: PSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In nuclear medicine, theranostics is a burgeoning development that is rapidly being implemented worldwide. There is an increasing need to provide a multidisciplinary framework to the practice of theranostics, ensuring that patients receive this treatment safely and are secure in the knowledge that their health-care practitioners are adequately trained. Nuclear medicine experts in Australia have taken the initiative of producing a set of theranostic guidelines relevant to Australian medical practice. These guidelines encompass specialist qualifications, patient care, radiopharmaceutical production, radiation safety, and dosimetry. We propose adaptation of these guidelines by other countries, and we promote standards of practice leading to optimal clinical outcomes for patients receiving theranostic treatments., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: The objective of this study was to perform an intra-individual dual tracer comparison of Fluorodeoxyglucose (FDG) and Prostate Specific Membrane Antigen (PSMA) computed tomography (CT)/Positron Emission Tomography (PET) against standard of care (SOC) imaging for the characterisation, staging and restaging of renal cell carcinoma (RCC)., Methods: A multicentre retrospective cohort study was performed at 3 major tertiary referral institutions in Brisbane, Australia between 2015 and 2020. All patients who underwent both PSMA and FDG PET/CT following SOC imaging for investigation of RCC were identified. Clinical details, imaging characteristics and histopathology were collected prior to univariate statistical analysis., Results: Eleven patients who underwent dual tracer PET/CT were included. Mean age was 65.5 years (SD 8.8). Most patients were male (64%) with clear cell morphology (91%). The indication for dual tracer PET was staging (36%) and restaging after radical/partial nephrectomy (64%). Primary tumour assessment showed mixed avidity patterns (concordant 40%, discordant favouring PSMA 20%, and FDG 40%). Metastatic disease assessment showed concordant avidity in 6 patients (55%), concordant negative in 3 (27%), and discordant uptake favouring PSMA. PET outperformed SOC imaging for assessment of metastatic disease in 5 patients (45%) and equivalent for the remainder. A change in management was noted in three cases (27%)., Conclusion: Dual tracer FDG and PSMA PET/CT for assessment of primary and metastatic RCC were mostly concordant. PET imaging outperformed conventional imaging and led to a change in management for 1 in 4 patients. Further studies with larger samples sizes are required to validate these findings and identify characteristics to guide patient selection for selective or dual tracer use., Competing Interests: Conflict of interests The authors have no conflicts of interests to declare that are relevant to the content of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: [ 18 F]PSMA-1007 has potential advantages over [ 68  Ga]Ga-PSMA-11, although limited prospective data evaluating diagnostic performance exist. The aims of this study are to describe the concordance of [ 18 FPSMA-1007 and [ 68  Ga]Ga-PSMA-11 for TNM with the American Joint Committee on Cancer (AJCC) prognostic stage and assess differences in tracer uptake., Methods: Fifty men (mean age 71.8) were imaged with [ 68  Ga]Ga-PSMA-11 and [ 18 F]PSMA-1007 < 4 weeks apart. Images were independently reported according to TNM by two experienced nuclear medicine specialists blinded to the other scan and prior imaging. Discordant results were resolved by a third independent nuclear medicine specialist. Quantitative analysis of lesion uptake and physiologic tissue for each tracer was performed by one experienced reader., Results: Scan indications were initial staging (n = 12), biochemical recurrence (n = 27) and metastatic disease evaluation (n = 11). Most patients had ISUP grade group 3 or higher. Median PSA value was 2.7 ng/ml (IQR 0.7-12.0), and a minority of patients (28%) were currently treated with androgen deprivation therapy. [ 18 F]PSMA-1007 uptake was significantly higher than [ 68 Ga]Ga-PSMA-11 in local recurrence, nodal and distant metastases and most physiologic sites (including bone) except for urinary bladder which was significantly lower. [ 18 F]PSMA-1007 upstaged local prostate staging in 5/17 patients, local recurrence in 3/33 patients, regional nodal disease in 3/50 patients and 1 distant metastasis (bladder). [ 68 Ga]Ga-PSMA-11 upstaged regional nodal disease in 1/50 patients and distant metastasis in one patient (right adrenal). Overall AJCC prognostic stage was concordant in 46/50 (92%) patients, with two patients upstaged for both [ 18 F]PSMA-1007 and [ 68 Ga]Ga-PSMA-11. [ 18 F]PSMA-1007 had more equivocal results (one regional node; six equivocal bone lesions, one of which was subsequently confirmed metastatic) than [ 68 Ga]Ga-PSMA-11 (one equivocal local recurrence)., Conclusion: Overall AJCC prognostic stage was similar (92%) between [ 18 F]PSMA-1007 and [ 68 Ga]Ga-PSMA-11. [ 18 F]PSMA-1007 demonstrates higher uptake within involved nodes and distant metastases and most physiologic sites except urinary bladder which aided [ 18 F]PSMA-1007 local staging of the prostate primary/local recurrence and regional nodal disease adjacent ureters. However, [ 18 F]PSMA-1007 liver uptake obscured a solitary right adrenal metastasis, and more equivocal bone lesions were identified. Trial registration The study was registered with Australia New Zealand Clinical Trials Registry (ACTRN12618000665235) on 24 April 2018., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [ 68 Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [ 18 F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [ 18 F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis., Results: The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease., Conclusion: Metastatic disease according to [ 18 F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [ 18 F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax., (© 2021. The Author(s).)

Background: Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for false negative concerns. In addition, 68 Ga-PSMA-11 positron emission tomography/computed tomography (prostate-specific membrane antigen [PSMA]) may also identify csPCa accurately., Objective: This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa., Design, Setting, and Participants: A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy., Outcome Measurements and Statistical Analysis: Sensitivity, specificity, and predictive values (negative predictive value [NPV] and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy., Results and Limitations: Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3-5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 [1.11-1.39], p < 0.001). Sensitivity also improved (97% vs 83%, p < 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall., Conclusions: PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging., Patient Summary: The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: [ 18 F]PSMA-1007 offers advantages of low urinary tracer excretion and theoretical improved spatial resolution for imaging prostate cancer. However, non-specific bone lesions (NSBLs), defined as mild to moderate focal bone uptake without a typical morphological correlate on CT, are a common finding on [ 18 F]PSMA-1007 PET/CT. The purpose of this study was to investigate the clinical outcomes of patients with [ 18 F]PSMA-1007 avid NSBLs, to determine whether patients with NSBLs represent a higher risk clinical cohort, and to determine whether SUVmax can be used as a classifier of bone metastasis., Methods: A retrospective audit of 214 men with prostate cancer was performed to investigate the clinical outcomes of [ 18 F]PSMA-1007 avid NSBLs according to defined criteria. We also compared the serum PSA, Gleason score, and uptake time of patients with [ 18 F]PSMA-1007 avid NSBLs to patients without [ 18 F]PSMA-1007 avid bone lesions. Finally, we analysed an SUVmax threshold to identify bone metastases using ROC curve analysis., Results: Ninety-four of 214 patients (43.9%) demonstrated at least one NSBL. No [ 18 F]PSMA-1007 avid NSBLs met criteria for a likely malignant or definitely malignant lesion after a median 15.8-month follow-up interval (11.9% definitely benign, 50.3% likely benign, and 37.7% equivocal). There were no statistically significant differences in serum PSA, Gleason score, and uptake time between patients with [ 18 F]PSMA-1007 avid NSBLs and those without [ 18 F]PSMA-1007 avid bone lesions. All NSBLs with adequate follow-up had SUVmax ≤ 11.1. The value of the highest SUVmax distinguished between NSBLs and definite prostate cancer bone metastases, whereby an SUVmax threshold of ≥ 7.2 maximized the Youden's index., Conclusion: [ 18 F]PSMA-1007 avid NSBLs rarely represent prostate cancer bone metastases. When identified in the absence of definite metastatic disease elsewhere, it is appropriate to classify those with SUVmax < 7.2 as likely benign. NSBLs with SUVmax 7.2-11.1 may be classified as equivocal or metastatic, with patient clinical risk factors, scan appearance, and potential management implications used to guide interpretation., (© 2021. Crown.)

Background: Because management is very different, it is important to differentiate between small focal insulinomas and diffuse pancreatic dysplasia (nesidioblastosis) in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia (EHH). Most insulinomas highly express glucagon-like peptide-1 receptors enabling positron emission tomography-computed tomography imaging with its radiolabelled analogue; 68 Ga-DOTA-Exendin-4 (Exendin)., Aim: To determine: (i) the utility of Exendin in EHH patients in a clinical setting; and (ii) whether the degree of Exendin uptake differentiates non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) from post-gastric bypass hypoglycaemia (PGBH)., Methods: This retrospective study reviewed the clinical, biochemistry and prior imaging findings in confirmed EHH patients referred for Exendin. Accuracy of Exendin was based on surgical findings and treatment outcomes. Finally, average Exendin uptake (SUVmax) of five PGBH studies was compared with the SUVmax of a key NIPHS case report., Results: Twenty of 25 consecutive patients had confirmed EHH. Exendin located insulinomas in eight of nine patients enabling successful surgical excision with rapid and durable cure. Exendin correctly identified diffuse nesidioblastosis in two of three cases requiring partial pancreatectomy for hypoglycaemia control. All three relapsed within 1.7 years with one needing completion pancreatectomy. Establishing the cause in the remainder relied on other investigations, clinical correlation and response to empirical treatment. Finally, Exendin SUVmax could not distinguish between NIPHS and PGBH., Conclusion: In EHH patients, Exendin accurately identifies the site of insulinoma and thereby differentiates it from nesidioblastosis but negative findings should not be ignored. Exendin is unlikely to differentiate between normal pancreatic uptake, NIPHS and PGBH., (© 2020 Royal Australasian College of Physicians.)

Objective: To assess the activity and safety of sequential lutetium-177 ( 177 Lu)-PSMA-617 and docetaxel vs docetaxel on a background of androgen deprivation therapy (ADT) in men with de novo metastatic hormone-naïve prostate cancer (mHNPC)., Patients and Methods: UpFrontPSMA (NCT04343885) is an open-label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: prostate cancer with a histological diagnosis within 12 weeks of screening commencement; prostate-specific antigen (PSA) >10 ng/mL at diagnosis; ≤4 weeks on ADT; evidence of metastatic disease on computed tomography (CT) and/or bone scan; high-volume prostate-specific membrane antigen (PSMA)-avid disease with a maximum standardized uptake value >15; and absence of extensive discordant fluorodeoxyglcuose (FDG)-positive, PSMA-negative disease. 68 Ga-PSMA-11 and 18 F-FDG positron-emission tomography (PET)/CT undergo central review to determine eligibility. Patients are randomized 1:1 to experimental treatment, Arm A ( 177 Lu-PSMA-617 7.5GBq q6w × 2 cycles followed by docetaxel 75 mg/m 2 q3w × 6 cycles), or standard-of-care treatment, Arm B (docetaxel 75 mg/m 2 q3w × 6 cycles). All patients receive continuous ADT. Patients are stratified based on disease volume on conventional imaging and duration of ADT at time of registration. The primary endpoint is the proportion of patients with undetectable PSA (≤0.2 ng/L) at 12 months after study treatment commencement. Secondary endpoints include safety, time to castration resistance, overall survival, PSA and radiographic progression-free survival, objective tumour response rate, early PSMA PET response, health-related quality of life, and frequency and severity of adverse events. Enrolment commenced in April 2020., Results and Conclusions: The results of this trial will generate data on the activity and safety of 177 Lu-PSMA-617 in men with de novo mHNPC in a randomized phase 2 design., (© 2021 The Authors BJU International © 2021 BJU International Published by John Wiley & Sons Ltd.)

Abstract: A 69-year-old woman presented with symptomatic hypercalcemia and deranged liver function. 18F-FDG PET/CT showed intense confluent avidity throughout the hepatic parenchyma, which was an isolated abnormality. Subsequent MRI demonstrated a diffuse infiltrative hepatic abnormality, with percutaneous liver biopsy findings consistent with hepatic sarcoidosis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

PSMA PET is more accurate than conventional imaging (CT/bone scan) for staging of intermediate- or high-risk prostate cancer (PCa), but 5-10% of primary tumours have low PSMA ligand uptake. FDG PET has been used to further define disease extent in end-stage castrate-resistant PCa and may be beneficial earlier in the disease course for more accurate staging. The objective of this study was to review the available evidence for patients undergoing both FDG and PSMA PET for PCa staging at initial diagnosis and in recurrent disease. A systematic literature review was performed for studies with direct, intraindividual comparison of PSMA and FDG PET for staging of PCa. Assessment for radioligand therapy eligibility was not considered. Risk of bias was assessed. 543 citations were screened and assessed. 13 case reports, three retrospective studies, and one prospective study were included. FDG after PSMA PET improved the detection of metastases from 65% to 73% in high-risk early castration-resistant PCa with negative conventional imaging (M0). Positive FDG PET was found in 17% of men with negative PSMA PET for postprostatectomy biochemical recurrence. Gleason score ≥8 and higher PSA levels predicted FDG-avid metastases in BCR and primary staging. Variant histology (ductal and neuroendocrine) was common in case reports, resulting in PSMA-negative FDG-positive imaging for 3 patients. Dual-tracer PET for PCa may assist in characterising high-risk disease during primary staging and restaging. Further studies are required to determine the additive benefit of FDG PET and if the FDG-positive phenotype may indicate a poorer prognosis., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Stephen McGeorge et al.)

Phaeochromocytomas and paragangliomas (PPGLs) are rare tumours that arise from the adrenal medulla or extra-adrenal sympathetic or parasympathetic paraganglia. Recent advances in genetics have greatly enhanced understanding of the pathogenesis and molecular physiology of PPGL. Concomitantly, advances in molecular imaging mean four techniques are now available for use in PPGLs: [ 123 I]-MIBG coupled with SPECT/CT; [ 18 F]- FDG, [ 68 Ga]-DOTATATE and [ 18 F]-FDOPA coupled with PET/CT. Each modality relies on unique cellular uptake mechanisms that are contingent upon the tumour's molecular behaviour-which, in turn, is determined by the tumour's genetic profile. This genotype-phenotype correlation means the appropriate choice of radiotracer may depend on the known (or suspected) underlying genetic mutation, in addition to the clinical indication for the scan-whether confirming diagnosis, staging disease, surveillance or determining eligibility for radionuclide therapy. Given these rapid recent changes in genetic understanding and molecular imaging options, many clinicians find it challenging to choose the most appropriate scan for an individual with PPGL. To this end, recent guidelines published by the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging (EANM/SNMMI) have detailed the preferred radiotracer choices for individuals with PPGL based on their genotype and/or clinical presentation, providing timely clarity in this rapidly moving field. The current review summarizes the implications of the genotype-phenotype relationship of PPGL, specifically relating this to the performance of molecular imaging modalities, to inform and enable practising endocrinologists to provide tailored, personalized care for individuals with PPGL., (© 2020 John Wiley & Sons Ltd.)

Abstract: Metastasis to the pancreas from differentiated thyroid carcinoma is rare. A new pancreatic lesion was identified on surveillance imaging of a man with metastatic papillary thyroid carcinoma 7 years after initial diagnosis. Imaging with 124I-PET/CT was performed to noninvasively confirm metastatic thyroid cancer and provide prospective dosimetry to guide selection of a safe and effective administered activity of 131I. This case demonstrates the emerging role of 124I-PET/CT as a useful diagnostic scan, pretherapy scan, and dosimetric tool to deliver personalized therapy for patients with metastatic thyroid cancer., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lutetium-177 [ 177 Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [ 177 Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer., Methods: We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [ 68 Ga]Ga-PSMA-11 and 2-flourine-18[ 18 F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [ 177 Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m 2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428., Findings: Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [ 177 Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [ 177 Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9-37]; p=0·0016). Grade 3-4 adverse events occurred in 32 (33%) of 98 men in the [ 177 Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [ 177 Lu]Lu-PSMA-617., Interpretation: [ 177 Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [ 177 Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel., Funding: Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) improves prostate cancer staging. Intraprostatic PSMA intensity may predict clinically relevant oncological outcomes. The aim of this study was to investigate the relationship between intraprostatic PSMA intensity and adverse pathology outcomes, including biochemical progression-free survival (PFS) after radical prostatectomy., Methods: This is a cohort study of 71 patients with MRI-guided, biopsy-proven prostate cancer and pre-operative 68 Ga-PSMA-11 PET/CT prior to radical prostatectomy (RP). Intraprostatic PSMA intensity was correlated to adverse pathology outcomes (Gleason score and upgrading from biopsy, pathological stage) and PFS using multivariate statistical analysis., Results: 68 Ga-PSMA-11 PET/CT intensity in vivo predicted all of Gleason score on RP, upgrading from biopsy to RP histopathology, pathological stage, positive surgical margins and PFS. 74.6% (53/71) of patients were free from progression at a median follow-up of 19.5 months (0.4-48 months). Predictive accuracy was particularly enhanced by PSMA among patients with biopsy Gleason score ≤ 3 + 4 (n = 39) as the most significant predictor of PFS according to Cox-proportional hazards regression. Cox-regression adjusted survival analysis predicted a 5.48-fold increase in hazard for Gleason score ≤ 3 + 4 patients with high (SUVmax > 8) compared with low (SUVmax < 8) PSMA intensity., Conclusion: Intraprostatic 68 Ga-PSMA-11 intensity is prognostic and may be a valuable new biomarker in localised prostate cancer, especially in men with biopsy-proven Gleason 3 + 4 disease considering an initial approach of active surveillance or focal therapy.

Background: Positron Emission Tomography with Computed Tomography (PET/CT) is widely used in the assessment of many diseases, particularly including cancer. However, many factors can affect image quality and diagnostic performance of PET scans using FDG or other PET probes., Main Body: The aim of this pictorial essay is to review PET/CT protocols that can be useful to overcome these confounding factors in routine clinical situations, with a particular focus on pharmacological interventions and problem-oriented CT acquisition protocols., Conclusion: Imaging protocols and representative cases will be discussed, in addition to potential contraindications and precautions to be taken.

177 Lu-PSMA-617 is a radioligand with high affinity for prostate-specific membrane antigen (PSMA), enabling targeted β-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castration-resistant prostate cancer. We now report their longer-term outcomes, including a 20-patient extension cohort and outcomes of subsequent systemic treatments after completion of trial therapy. Methods: Fifty patients with PSMA-avid metastatic castration-resistant prostate cancer who had progressed after standard therapies received up to 4 cycles of 177 Lu-PSMA every 6 wk. Endpoints included prostate-specific antigen (PSA) response (Prostate Cancer Working Group 2), toxicity (Common Terminology Criteria for Adverse Events, version 4.03), imaging response, patient-reported health-related quality of life, progression-free survival, and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including 177 Lu-PSMA. Results: Seventy-five men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 mo) and extensive prior treatment, including prior docetaxel (84%), cabazitaxel (48%), and abiraterone or enzalutamide (92%). The mean administered radioactivity was 7.5 GBq/cycle. A PSA decline of at least 50% was achieved in 32 of 50 patients (64%; 95% confidence interval [CI], 50%-77%), including 22 patients (44%; 95% CI, 30%-59%) with at least an 80% decrease. Of 27 patients with measurable soft-tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to 177 Lu-PSMA were self-limiting G1-G2 dry mouth (66%), transient G1-G2 nausea (48%), G3-G4 thrombocytopenia (10%), and G3 anemia (10%). Brief Pain Inventory severity and interference scores decreased at all time points, including at the 3-mo follow-up, with a decrease of -1.2 (95% CI, -0.5 to -1.9; P = 0.001) and -1.0 (95% CI, -0.2 to -0.18; P = 0.013), respectively. At a median follow-up of 31.4 mo, median overall survival was 13.3 mo (95% CI, 10.5-18.7 mo), with a significantly longer survival of 18.4 mo (95% CI, 13.8-23.8 mo) in patients achieving a PSA decline of at least 50%. At progression after prior response, further 177 Lu-PSMA was administered to 15 (30%) patients (median of 2 cycles commencing 359 d from enrollment), with a PSA decline of at least 50% in 11 patients (73%). Four of 21 patients (19%) receiving other systemic therapies on progression experienced a PSA decline of at least 50%. There were no unexpected adverse events with 177 Lu-PSMA retreatment. Conclusion: This expanded 50-patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity, and improved quality of life with 177 Lu-PSMA radioligand therapy. On progression, rechallenge 177 Lu-PSMA demonstrated higher response rates than other systemic therapies., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Some patients with metastatic differentiated thyroid cancer (DTC) lack iodine avidity and are therefore unsuitable for radioactive iodine (RAI) therapy. Limited experience suggests that single-agent selective mitogen-activated protein kinase (MAPK) pathway inhibitors can restore expression of the sodium-iodide symporter rendering RAI refractory (RAIR) DTC patients amenable to RAI therapy. The aim of this study was to assess the feasibility of mutation-guided MAPK-pathway blockade combined with thyroid hormone withdrawal (THW) for redifferentiation. Methods: This is a retrospective review of metastatic RAIR DTC and driver mutation in MAPK pathway, treated on a redifferentiation protocol. All patients had metastatic disease that had never been RAI-avid and/or imaging and biochemical progression despite treatment with RAI within the past 12 months. Patients with tumors harboring an NRAS mutation were treated with an MEK inhibitor (trametinib), and tumors with a BRAF V600E mutation with combined BRAF and MEK inhibition (dabrafenib and trametinib; or vemurafenib and cobimetinib) for four weeks. Thyrotropin stimulation was performed by THW for four weeks. Restoration of RAI uptake was determined by 124 I positron emission tomography/computed tomography imaging. The response was assessed at least three months post-RAI. Results: From 2015 to 2017, six patients (age 45-70, four females) received redifferentiation therapy. Three patients had an NRAS mutation; two with follicular thyroid carcinoma (FTC) and one with a poorly differentiated thyroid carcinoma (PDTC); and three patients had a BRAF V600E mutation and papillary thyroid carcinoma (PTC). One NRAS and all BRAF V600E mutation cases demonstrated restoration of RAI uptake and proceeded to RAI therapy with a median follow-up of 16.6 months (range 13.5-42.3 months). The patient with an NRAS mutation and two of three patients with a BRAF V600E demonstrated partial imaging response beyond a three-month follow-up. Grade 3 adverse events (acneiform rash) were observed in two patients with NRAS mutations. Conclusions: Mutation-guided MAPK pathway inhibition with MEK inhibitor or a combination of BRAF inhibitor and MEK inhibitor under concurrent THW is a feasible and a promising strategy to redifferentiate RAIR DTC, thereby rendering them suitable for RAI therapy with satisfactory retention following treatment.

Imaging of somatostatin receptor expression is an established technique for staging of neuroendocrine neoplasia and determining the suitability of patients for peptide receptor radionuclide therapy. PET/CT using 68 Ga-labeled somatostatin analogs is superior to earlier agents, but the rapid physical decay of the radionuclide poses logistic and regulatory challenges. 64 Cu has attractive physical characteristics for imaging and provides a diagnostic partner for the therapeutic radionuclide 67 Cu. Based on promising preclinical studies, we have performed a first-time-in-humans trial of 64 Cu-MeCOSar-Tyr 3 -octreotate ( 64 Cu-SARTATE) to assess its safety and ability to localize disease at early and late imaging time-points. Methods: In a prospective trial, 10 patients with known neuroendocrine neoplasia and positive for uptake on 68 Ga-DOTA-octreotate ( 68 Ga-DOTATATE) PET/CT underwent serial PET/CT imaging at 30 min, 1 h, 4 h, and 24 h after injection of 64 Cu-SARTATE. Adverse reactions were recorded, and laboratory testing was performed during infusion and at 1 and 7 d after imaging. Images were analyzed for lesion and normal-organ uptake and clearance to assess lesion contrast and perform dosimetry estimates. Results: 64 Cu-SARTATE was well tolerated during infusion and throughout the study, with 3 patients experiencing mild infusion-related events. High lesion uptake and retention were observed at all imaging time-points. There was progressive hepatic clearance over time, providing the highest lesion-to-liver contrast at 24 h. Image quality remained high at this time. Comparison of 64 Cu-SARTATE PET/CT obtained at 4 h to 68 Ga-DOTATATE PET/CT obtained at 1 h indicated comparable or superior lesion detection in all patients, especially in the liver. As expected, the highest early physiologic organ uptake was in the kidneys, liver, and spleen. Conclusion: 64 Cu-SARTATE is safe and has excellent imaging characteristics. High late-retention in tumor and clearance from the liver suggest suitability for diagnostic studies and for prospective dosimetry for 67 Cu-SARTATE peptide receptor radionuclide therapy, and the half-life of 64 Cu would also facilitate good-manufacturing-practice production and distribution to sites without access to 68 Ga., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Hyperglycaemia can influence 18 F-fluorodeoxyglucose (FDG) uptake due to competition for glucose transport and phosphorylation by hexokinase. Major international nuclear medicine societies recommend blood glucose level (BGL) < 11.1 mmol/L (200 mg/dL) prior to performing FDG positron emission tomography/computed tomography (PET/CT). However, there is no consensus approach and complications of previously proposed insulin guidelines included significant hypoglycaemia, inconvenience and skeletal muscle uptake. This study aims to establish the safety and efficacy of a personalised insulin calculator protocol to estimate the dose of intravenous insulin injection for correction of hyperglycaemia prior to FDG PET/CT., Results: This is a retrospective audit of all patients treated with insulin for hyperglycaemia (BGL > 10 mmol/L) prior to FDG PET/CT at the Peter MacCallum Cancer Centre over a 2-year period. Cohort 1 comprised a 12-month period (April 1, 2014-March 31, 2015) using the department's established empiric-dose insulin protocol, and Cohort 2 the 12 months (April 1, 2015-March 31, 2016) following introduction of a personalised insulin calculator protocol. Variables including body mass index, insulin-dose calculated and/or administered, BGL at baseline and nadir, and time to FDG injection were analysed. There were 115 and 136 patients treated with insulin in Cohorts 1 and 2 respectively, with similar baseline variables including mean BGL (14.5 vs 14.4 mmol/L) and range (10.5-22.7 vs 10.4-24.3 mmol/L). Use of the new personalised insulin calculator resulted in significantly fewer hypoglycaemic events (0.7% vs 5.2%; P < 0.03), shorter median time from insulin to FDG injections (108 min vs 136 min; P < 0.001) and greater individualised range in insulin prescription (3-32 IU vs 4-20 IU). The majority of patients (88.3%) receiving the personalised insulin calculator prescribed dose achieved BGL < 10.0 mmol/L. All scans obtained were of diagnostic quality., Conclusions: The use of our personalised insulin calculator protocol effectively lowered BGL to the target range, resulted in significantly fewer hypoglycaemic events and reduced median time between insulin and FDG injection compared to a pre-existing empiric protocol whilst achieving diagnostic scans.

18 F-FDG-avid thyroid incidentaloma (TI) is seen in approximately 2.5% of patients imaged for staging or response assessment of malignancy and represents thyroid cancer in approximately 35% of cases. Consequently, the 2015 American Thyroid Association guidelines strongly recommend investigation of all 18 F-FDG-avid nodules 1 cm or larger with ultrasound and fine-needle aspiration cytology (FNA). This study aimed to assess the overall and thyroid cancer-specific survival in a large cohort of patients with 18 F-FDG-avid TI with long-term follow-up to assess the validity of this approach. Methods: Retrospective review of 45,680 PET/CT scans performed at a comprehensive cancer center from January 2007 to January 2015 identified 2,588 18 F-FDG PET/CT reports referring to the thyroid. After exclusion of nonavid thyroid nodules, diffuse 18 F-FDG uptake, known thyroid cancer, abnormalities adjacent to the thyroid, and repeat studies, 500 patients (1.1%) with TI were identified, of whom 362 had confirmed death or more than 12 mo of clinical follow-up. Variables including age, sex, primary malignancy, overall survival, thyroid cancer-specific survival, FNA, and histopathology were collected until January 2016. Multivariate logistic regression and survival analysis were performed. Results: The 362 analyzed patients (65% female) had a median age of 65 y (range, 19-96 y) and follow-up of 24 mo (range, 1-103 mo). Lymphoid, lung, and colorectal malignancy were the most common staging indications. Median overall survival was 20 mo (interquartile range, 9.5-39 mo). Most of the 180 observed deaths were due to the primary malignancy under investigation (92.2%) or to causes not related to cancer (7.2%); one patient (0.6%) died from incidentally detected medullary thyroid cancer. 18 F-FDG avidity in the index malignancy, an advanced stage for that malignancy, and a clinician decision not to investigate 18 F-FDG-avid TI were all predictors of mortality, with hazard ratios of 8.5, 3.0, and 3.3, respectively, and 95% confidence intervals of 4.6-15.8, 2.3-3.9, and 2.0-5.0, respectively ( P < 0.001). Of 131 patients suitable for cytologic or histopathologic evaluation, 47 (36%) had incidental thyroid cancer (24 papillary, 11 malignant FNA, 5 oncocytic/Hürthle cell, 2 medullary, 1 follicular, and 4 metastases from underlying malignancy). Conclusion: Overall survival with 18 F-FDG-avid TI was poor because of the prognosis associated with underlying malignancy, which must be considered before investigation of 18 F-FDG-avid TI and certainly before aggressive treatment. Active surveillance should be considered in this group of patients., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Lymphangitic carcinomatosis refers to the rare process of diffuse malignant invasion of the pulmonary lymphatics. We describe the first reported case of lymphangitic carcinomatosis visualized with gallium-68 prostate-specific membrane antigen positron emission tomography and its clinical significance in a 53-year-old man with prostate carcinoma. This case highlights the ability of gallium-68 prostate-specific membrane antigen positron emission tomography for prostate carcinoma characterization and the importance of always considering atypical patterns of metastatic disease., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)