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Background: Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows f

Purpose: Lutetium-177 [ 177 Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [ 177 Lu]Lu-PSMA-617., Methods: In this retrospective study, 68 men with progressive mCRPC treated with [ 177 Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [ 177 Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [ 177 Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [ 177 Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUV max and SUV mean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates., Results: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [ 177 Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUV max or SUV mean did not correlate with PSA-PFS or OS., Conclusion: We successfully implemented same-day post-therapy SPECT/CT after [ 177 Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the feasibility of using the StarGuide (General Electric Healthcare, Haifa, Israel), a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177 Lu-labeled radiopharmaceuticals., Methods: Thirty-one patients (34-89 years old; mean ± SD, 65.5 ± 12.1) who were treated with either 177 Lu-DOTATATE (n=17) or 177 Lu-PSMA617 (n=14) as part of standard of care were scanned post-therapy with the StarGuide; some were also scanned with the standard GE Discovery 670 Pro SPECT/CT. All patients had either 64 Cu-DOTATATE or 18 F-DCFPyL PET/CT prior to first cycle of therapy for eligibility check. The detection/targeting rate (lesion uptake greater than blood pool uptake) of large lesions meeting RECIST 1.1 size criteria on post-therapy StarGuide SPECT/CT was evaluated and compared to the standard design GE Discovery 670 Pro SPECT/CT (when available) and pre-therapy PET by two nuclear medicine physicians with consensus read., Results: This retrospective analysis identified a total of 50 post-therapy scans performed with the new imaging protocol from November 2021 to August 2022. The StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The pre-therapy 64 Cu-DOTATATE PET takes 20 min with 4 bed positions on GE Discovery MI PET/CT, and 18 F-DCFPyL PET takes 8-10 min with 4-5 bed positions on GE Discovery MI PET/CT. This preliminary evaluation showed that the post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system and detected large lesions defined by RECIST criteria on the pre-therapy PET scans., Conclusion: Fast acquisition of whole-body post-therapy SPECT/CT is feasible with the new StarGuide system. Short scanning time improves the patients' clinical experience and compliance which may lead to increased adoption of post-therapy SPECT. This opens the possibility to offer imaged-based treatment response assessment and personalized dosimetry to patients referred for targeted radionuclide therapies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20%-65% of highly suspicious lesions on mpMRI (PI-RADS [Prostate Imaging-Reporting and Data System] 4 or 5) are false-positives (FPs), while 5%-10% of clinically significant PC (csPC) are missed. Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPRs) are both overexpressed in PC. We therefore aimed to evaluate the potential of 68 Ga-PSMA11 and 68 Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC. Methods: A highly selective cohort of 13 men, aged 58.0 ± 7.1 y, with suspected PC (persistently high prostate-specific antigen [PSA] and PSA density) but negative or equivocal mpMRI results or negative biopsy were prospectively enrolled to undergo 68 Ga-PSMA11 and 68 Ga-RM2 PET/MRI. PET/MRI included whole-body and dedicated pelvic imaging after a delay of 20 min. All patients had targeted biopsy of any lesions seen on PET followed by standard 12-core biopsy. The SUV max of suspected PC lesions was collected and compared with gold standard biopsy. Results: PSA and PSA density at enrollment were 9.8 ± 6.0 (range, 1.5-25.5) ng/mL and 0.20 ± 0.18 (range, 0.06-0.68) ng/mL 2 , respectively. Standardized systematic biopsy revealed a total of 14 PCs in 8 participants: 7 were csPC and 7 were nonclinically significant PC (ncsPC). 68 Ga-PSMA11 identified 25 lesions, of which 11 (44%) were true-positive (TP) (5 csPC). 68 Ga-RM2 showed 27 lesions, of which 14 (52%) were TP, identifying all 7 csPC and also 7 ncsPC. There were 17 concordant lesions in 11 patients versus 14 discordant lesions in 7 patients between 68 Ga-PSMA11 and 68 Ga-RM2 PET. Incongruent lesions had the highest rate of FP (12 FP vs. 2 TP). SUV max was significantly higher for TP than FP lesions in delayed pelvic imaging for 68 Ga-PSMA11 (6.49 ± 4.14 vs. 4.05 ± 1.55, P = 0.023) but not for whole-body images, nor for 68 Ga-RM2. Conclusion: Our results show that 68 Ga-PSMA11 and 68 Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC. Both radiopharmaceuticals detected additional clinically significant cancers not seen on mpMRI in this selective cohort. 68 Ga-RM2 PET/MRI identified all csPC confirmed at biopsy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Focal therapy for localized prostate cancer (PC) using high-intensity focused ultrasound (HIFU) is gaining in popularity as it is noninvasive and associated with fewer side effects than standard whole-gland treatments. However, better methods to evaluate response to HIFU ablation are an unmet need. Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in PC. In this study, we evaluated a novel approach of using both 68 Ga-RM2 and 68 Ga-PSMA11 PET/MRI in each patient before and after HIFU to assess the accuracy of target tumor localization and response to treatment. Methods: Fourteen men, 64.5 ± 8.0 y old (range, 48-78 y), with newly diagnosed PC were prospectively enrolled. Before HIFU, the patients underwent prostate biopsy, multiparametric MRI, 68 Ga-PSMA11, and 68 Ga-RM2 PET/MRI. Response to treatment was assessed at a minimum of 6 mo after HIFU with prostate biopsy ( n  = 13), as well as 68 Ga-PSMA11 and 68 Ga-RM2 PET/MRI ( n  = 14). The SUV max and SUV peak of known or suspected PC lesions were collected. Results: Pre-HIFU biopsy revealed 18 cancers, of which 14 were clinically significant (Gleason score ≥ 3 + 4). Multiparametric MRI identified 18 lesions; 14 of them were at least score 4 in the Prostate Imaging-Reporting and Data System. 68 Ga-PSMA11 and 68 Ga-RM2 PET/MRI each showed 23 positive intraprostatic lesions; 21 were congruent in 13 patients, and 5 were incongruent in 5 patients. Before HIFU, 68 Ga-PSMA11 identified all target tumors, whereas 68 Ga-RM2 PET/MRI missed 2 tumors. After HIFU, 68 Ga-RM2 and 68 Ga-PSMA11 PET/MRI both identified clinically significant residual disease in 1 patient. Three significant ipsilateral recurrent lesions were identified, whereas 1 was missed by 68 Ga-PSMA11. The pretreatment level of prostate-specific antigen decreased significantly after HIFU, by 66%. Concordantly, the pretreatment SUV max decreased significantly after HIFU for 68 Ga-PSMA11 ( P  = 0.001) and 68 Ga-RM2 ( P  = 0.005). Conclusion: This pilot study showed that 68 Ga-PSMA11 and 68 Ga-RM2 PET/MRI identified the target tumor for HIFU in 100% and 86% of cases, respectively, and accurately verified response to treatment. PET may be a useful tool in the guidance and monitoring of treatment success in patients receiving focal therapy for PC. These preliminary findings warrant larger studies for validation., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Abstract: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has shown great treatment efficacy in patients with well-differentiated metastatic neuroendocrine tumors and a metastatic size reduction of ~20% for metastatic lesions <3 cm in size. We present a 66-year-old man with pancreatic neuroendocrine carcinoma, who had a rapidly growing metastatic nodal conglomerate, which measured close to 10 cm in size. After only 2 cycles of PRRT with 177 Lu-DOTATATE, the nodal conglomerate had a striking size reduction greater than 75%. This case highlights the potential efficacy of PRRT with 177 Lu-DOTATATE for treatment of aggressive neuroendocrine neoplasms., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. This work was funded by the National Institutes of Health–National Cancer Institute (5T32CA00969)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale and Objectives: High-grade gastroenteropancreatic neuroendocrine neoplasms (G3 GEP-NENs) are pathologically classified into well differentiated neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (G3 NECs). Using a novel parameter, we examined the prognostic value of 18 F-FDG and 68 Ga-DOTATATE PET/CT quantification in comparison to pathologic assessment in G3 GEP-NENs., Materials and Methods: A total of 31 patients with G3 GEP-NENs were reviewed. For each patient, the SUVmax on 18 F-FDG and 68 Ga-DOTATATE PET/CT were used to calculate the FDG-DOTATATE-Z (FDZ) score: a continuous parameter that increases with 68 Ga-DOTATATE uptake and decreases with 18 F-FDG uptake. The variation in the FDZ score with respect to pathologic variables was examined. Kaplan-Meier and Cox regression analyses were performed to evaluate the effect of FDZ score on overall survival. An external cohort of 21 patients was used for validation., Results: The FDZ score was significantly higher in G3 NETs compared to G3 NECs (p<0.001), and was inversely correlated with Ki67 index (R 2 =0.33, p<0.001). Patients in the FDZ>0.05 group showed significantly longer survival compared to those in the FDZ≤0.05 group, with median of 34.9 vs. 12.0 months (p<0.001). On univariate regression, FDZ>0.05 (p=0.005), well differentiated disease (p=0.044), and lower Ki67 index (p=0.042) were predictors of survival. On multivariate regression, only FDZ>0.05 could independently predict longer survival with HR=0.16 (p=0.018), which was reproduced in the external validation cohort., Conclusion: Combined quantification of 18 F-FDG and 68 Ga-DOTATATE PET/CT into a novel parameter, the FDZ score, reflects the pathologic characteristics of G3 GEP-NENs and is a prognostic indicator of overall survival independent of differentiation., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells (usually cancer) using the same molecule, thus guaranteeing a targeted cytotoxic approach of the imaged tumor cells while sparing healthy tissues. As the brilliant late Sam Gambhir would say, the imaging agent acts like a 'molecular spy' and reveals where the tumoral cells are located and the extent of disease burden (diagnosis). For treatment, the same 'molecular spy' docks to the same tumor cells, this time delivering cytotoxic doses of radiation (treatment). This duality represents the concept of a 'theranostic pair', which follows the scope and fundamental principles of targeted precision and personalized medicine. Although the term theranostic was noted in medical literature in the early 2000s, the principle is not at all new to nuclear medicine. The first example of theranostic dates back to 1941 when Dr. Saul Hertz first applied radioiodine for radionuclide treatment of thyroid cells in patients with hyperthyroidism. Ever since, theranostics has been an integral element of nuclear medicine and molecular imaging. The more we understand tumor biology and molecular pathology of carcinogenesis, including specific mutations and receptor expression profiles, the more specific these 'molecular spies' can be developed for diagnostic molecular imaging and subsequent radionuclide targeted therapy (radiotheranostics). The appropriate selection of the diagnostic and therapeutic radionuclide for the 'theranostic pair' is critical and takes into account not only the type of cytotoxic radiation emission, but also the linear energy transfer (LET), and the physical half-lives. Advances in radiochemistry and radiopharmacy with new radiolabeling techniques and chelators are revolutionizing the field. The landscape of cytotoxic systemic radionuclide treatments has dramatically expanded through the past decades thanks to all these advancements. This article discusses present and promising future theranostic applications for various types of diseases such as thyroid disorders, neuroendocrine tumors (NET), pediatric malignancies, and prostate cancer (PC), and provides an outlook for future perspectives., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Our purpose was to investigate the prognostic value of 18 F-FDG PET/CT parameters in melanoma patients before beginning therapy with antibodies to the programmed cell death 1 receptor (anti-PD-1). Methods: Imaging parameters including SUV max , metabolic tumor volume, and the ratio of bone marrow to liver SUV mean (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. The association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data were compared between the high-BLR group (>median) and the low-BLR group (≤median). Results: Multivariate analyses demonstrated that BLR was an independent prognostic factor for progression-free and overall survival ( P = 0.017 and P = 0.011, respectively). The high-BLR group had higher white blood cell counts and neutrophil counts and a higher level of C-reactive protein than the low-BLR group ( P < 0.05). Conclusion: Patients with a high BLR were associated with poor progression-free and overall survival, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To evaluate the diagnostic performance and clinical utility of 18 F-fluciclovine PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC)., Methods: 18 F-Fluciclovine scans of 165 consecutive men with BCR after primary definitive treatment with prostatectomy (n = 102) or radiotherapy (n = 63) were retrospectively evaluated. Seventy patients had concurrent imaging with at least one other conventional modality (CT (n = 31), MRI (n = 31), or bone scan (n = 26)). Findings from 18 F-fluciclovine PET were compared with those from conventional imaging modalities. The positivity rate and impact of 18 F-fluciclovine PET on patient management were recorded. In 33 patients who underwent at least one other PET imaging ( 18 F-NaF PET/CT (n = 12), 68 Ga-PSMA11 PET/CT (n = 5), 18 F-DCFPyL PET/CT (n = 20), and 68 Ga-RM2 PET/MRI (n = 5)), additional findings were evaluated., Results: The overall positivity rate of 18 F-fluciclovine PET was 67 %, which, as expected, increased with higher prostate-specific antigen (PSA) levels (ng/ml): 15 % (PSA < 0.5), 50 % (0.5 ≤ PSA < 1), 56 % (1 ≤ PSA < 2), 68 % (2 ≤ PSA < 5), and 94 % (PSA ≥ 5), respectively. One hundred and two patients (62 %) had changes in clinical management based on 18 F-fluciclovine PET findings. Twelve of these patients (12 %) had lesion localization on 18 F-fluciclovine PET, despite negative conventional imaging. Treatment plans of 14 patients with negative 18 F-fluciclovine PET were changed based on additional PET imaging with a different radiopharmaceutical., Conclusion: 18 F-Fluciclovine PET/CT remains a useful diagnostic tool in the workup of patients with BCR PC, changing clinical management in 62 % of participants in our cohort., (© 2021. World Molecular Imaging Society.)

We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single 68 Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.2), were enrolled. Fifty-two out of ninety-four participants underwent SiPM PET/CT first and a total of 162 lesions were detected using both scanners. Forty-two out of ninety-four participants underwent conventional PET/CT first and a total of 108 lesions were detected using both scanners. Regardless of whether SiPM-based PET/CT was used first or second, maximum standardized uptake value (SUV max ) of lesions measured on SiPM was on average 20% higher when comparing two scanners with all enrolled patients, and the difference was statistically significant. SiPM-based PET/CT detected 19 more lesions in 13 patients compared with conventional PET/CT. No lesions were only identified by conventional PET/CT. In conclusion, we observed higher SUV max for lesions measured from SiPM PET/CT compared with conventional PET/CT regardless of the order of the scans. SiPM PET/CT allowed for identification of more lesions than conventional PET/CT. While delayed imaging can lead to higher SUV max in cancer lesions, in the series of lesions identified when SiPM PET/CT was used first, this was not the case; therefore, the data suggest superior performance of the SiPM PET/CT scanner in visualizing and quantifying lesions.

Purpose: The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18 F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs)., Methods: Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated., Results: The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P < 0.0001). The median OS in patients with high MTVpost (≥ 23.44) was 16 months (95% CI 12-32 months) as compared with more than 60 months in patients with low MTVpost (< 23.44) (P = 0.0003). A multivariate model including PET/CT parameters and known clinical prognostic factors revealed that MTVpost and the presence of central nervous system lesions were independent prognostic factors for OS (P = 0.0004, 0.0167, respectively). One pseudoprogression case (1.2%) was seen in this population and classified into the high MTVpost group., Conclusion: Whole-body metabolic tumor volume from PET scan acquired approximately 3 months following initiation of immunotherapy (MTVpost) is a strong prognostic indicator of OS in melanoma patients. Although the possibility of pseudoprogression must be considered whenever evaluating first restaging PET imaging, it only occurred in 1 patient in our cohort.

18 F-DCFPyL (2-(3-{1-carboxy-5-[(6- 18 F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of 18 F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52-91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy ( n = 42) or radiotherapy ( n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), 18 F-fluciclovine PET/CT (18), or 18 F-NaF PET (14). Findings from 18 F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18 F-DCFPyL PET/CT was recorded from clinical chart review. Results: 18 F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA < 0.5), 69% (0.5 ≤ PSA < 1), 100% (1 ≤ PSA < 2), 91% (2 ≤ PSA < 5), and 96% (PSA ≥ 5). 18 F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20 of 41 (49%) CT or MRI scans had findings congruent with 18 F-DCFPyL, whereas 18 F-DCFPyL PET was positive in 17 of 41 (41%) cases with negative CT or MRI findings. For bone imaging, 26 of 38 (68%) bone or 18 F-NaF PET scans were congruent with 18 F-DCFPyL PET, whereas 18 F-DCFPyL PET localized bone lesions in 8 of 38 (21%) patients with negative results on bone or 18 F-NaF PET scans. In 8 of 18 (44%) patients, 18 F-fluciclovine PET had located the same lesions as did 18 F-DCFPyL PET, whereas 5 of 18 (28%) patients with negative 18 F-fluciclovine findings had positive 18 F-DCFPyL PET findings and 1 of 18 (6%) patients with negative 18 F-DCFPyL findings had uptake in the prostate bed on 18 F-fluciclovine PET. In the remaining 4 of 18 (22%) patients, 18 F-DCFPyL and 18 F-fluciclovine scans showed different lesions. Lastly, 43 of 72 (60%) patients had treatment changes after 18 F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18 F-DCFPyL PET, despite negative results on conventional imaging. Conclusion: 18 F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent PC, given the high positivity rate as compared with Food and Drug Administration-approved currently available imaging modalities and its impact on clinical management in 60% of patients., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

PET using radiolabeled prostate-specific membrane antigen (PSMA) is now being more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, 3 different criteria for interpretation of PSMA PET were published: the European Association of Nuclear Medicine (EANM) criteria, the Prostate Cancer Molecular Imaging Standardized Evaluation criteria, and the PSMA Reporting and Data System. We compared these 3 criteria in terms of interreader, intrareader, and intercriteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of 2 groups: 47 patients (mean age, 64.2 y old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)] ( 68 Ga-PSMA11) PET/MRI for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age, 70.5 y old) who underwent 68 Ga-PSMA11 PET/CT because of biochemically recurrent PC. Three nuclear medicine physicians independently evaluated all 68 Ga-PSMA11 PET/MRI and PET/CT studies according to the 3 interpretation criteria. Two of them reevaluated all studies 6 mo later in the same manner and masked to the initial reading. The Gwet agreement coefficient was calculated to evaluate interreader, intrareader, and intercriteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, interreader, intrareader, and intercriteria agreement ranged from substantial to almost perfect for any site according to all 3 criteria. In the PET/CT group, interreader agreement ranged from substantial to almost perfect except for judgment of distant metastases based on the PSMA Reporting and Data System (Gwet agreement coefficient, 0.57; moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intrareader agreement ranged from substantial to almost perfect for any site according to all 3 criteria. Intercriteria agreement for each site was also substantial to almost perfect. Conclusion: Although the 3 published criteria have good interreader and intrareader reproducibility in evaluating 68 Ga-PSMA11 PET, there are some factors causing interreader disagreement. Further work is needed to address this issue., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Molecular imaging enables both spatial and temporal understanding of the complex biologic systems underlying carcinogenesis and malignant spread. Single-photon emission tomography (SPECT) is a versatile nuclear imaging-based technique with ideal properties to study these processes in vivo in small animal models, as well as to identify potential drug candidates and characterize their antitumor action and potential adverse effects. Small animal SPECT and SPECT-CT (single-photon emission tomography combined with computer tomography) systems continue to evolve, as do the numerous SPECT radiopharmaceutical agents, allowing unprecedented sensitivity and quantitative molecular imaging capabilities. Several of these advances, their specific applications in oncology as well as new areas of exploration are highlighted in this chapter.

The diagnosis and subsequent therapy of neuroendocrine neoplasms (NENs) have long relied on somatostatin receptor (SSTR) expression. The field of theranostics now uses newer SSTR-based PET imaging with 68 Ga-DOTATATE or 68 Ga-DOTATOC as a prerequisite for the administration of peptide receptor radionuclide therapy (PRRT). In the United States, Food and Drug Administration approval of 177 Lu-DOTATATE, a form of PRRT, in 2018 for use in gastroenteropancreatic NENs was obtained on the basis of prolonged progression-free survival versus high-dose octreotide long-acting release in a phase III clinical trial of well-differentiated midgut NENs. Well-differentiated grade 1 and grade 2 NENs have a low proliferation index (Ki-67 < 20%) and longer overall survival (>10 y), whereas higher-grade (grade 3 [G3]) NENs have a high Ki-67 (>20%) and shorter overall survival (<1 y). Here, we present a review on the role of SSTR-based imaging and PRRT in G3 NENs, including a discussion of well-differentiated G3 NENs, the newest histologic classification. Some studies suggest that G3 NENs are less likely to be positive on SSTR-based imaging (but more likely on 18 F-FDG PET) than are well-differentiated NENs, but these data are limited. We found only 13 studies mentioning the use of PRRT in G3 NENs and a total of only 151 patients across these studies in whom radiologic response was measured. Of these 151 patients, 99 (66%) demonstrated at least stable disease or a partial response, indicating that some G3 NENs can be responsive to PRRT. We suggest that patients with G3 NENs should receive both 18 F-FDG PET and SSTR-based imaging to aid in both diagnosis and treatment selection, as positivity on SSTR-based imaging helps with patient identification for PRRT and discordance may suggest important clues to tumor biology and prognosis. However, prospective studies are needed to fully understand the role of PRRT in G3 NENs, especially in well- versus poorly differentiated G3 disease., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: The management of advanced or recurrent prostate cancer is limited in part by the lack of effective imaging agents. Metabolic changes in prostate cancer have previously been exploited for imaging, culminating in the recent US FDA approval of [ 11 C]choline for the detection of subclinical recurrent disease after definitive local therapy. Despite this milestone, production of [ 11 C]choline requires an on-site cyclotron, limiting the scope of medical centers at which this scan can be offered. In this pilot study, we tested whether prostate cancer could be imaged with positron emission tomography (PET) using [ 68 Ga]citrate, a radiotracer that targets iron metabolism but is produced without a cyclotron., Procedures: Eight patients with castrate-resistant prostate cancer were enrolled in this single-center feasibility study. All patients had evidence of metastatic disease by standard of care imaging [X-ray computed tomography (CT), bone scan, or magnetic resonance imaging (MRI)] prior to PET with [ 68 Ga]citrate. Patients were intravenously injected with increasing doses of [ 68 Ga]citrate (136.9 to a maximum of 259 MBq). Uptake time was steadily increased from 1 h to approximately 3.5 h for the final 4 patients, and all patients were imaged with a PET/MRI. Qualitative and semi-quantitative (maximum standardized uptake value (SUV max )) assessment of the metastatic lesions was performed and compared to the standard of care imaging., Results: At 1- and 2-h imaging times post injection, there were no detectable lesions with [ 68 Ga]citrate PET. At 3- to 4-h uptake time, there were a total of 71 [ 68 Ga]citrate-positive lesions (67 osseous, 1 liver, and 3 lymph node). Of these, 65 lesions were visible on the standard of care imaging (CT and/or bone scan). One PET-avid osseous vertebral body metastasis was not apparent on either CT or bone scan. Twenty-five lesions were not PET-avid but seen on CT and bone scan (17 bone, 6 lymph node, 1 pleural, and 1 liver). The average of the maximum SUVs for bone or soft tissue metastases for patients treated at higher doses and uptake time was statistically higher than the corresponding parameter in normal liver, muscle, and bone. Visually obvious blood pool activity was observed even 3-4 h post injection, suggesting that further optimization of the [ 68 Ga]citrate imaging protocol is required to maximize signal-to-background ratios., Conclusions: Our preliminary results support that PET with [ 68 Ga]citrate may be a novel tool for imaging prostate cancer. Future studies are needed to determine the optimal imaging protocol, the clinical significance of [ 68 Ga]citrate uptake, and its role in therapeutic decisions.

Many patients with hepatorenal syndrome (HRS) end up receiving a combined liver and kidney transplant (CKLT) with preservation of native kidneys, specially type 1 HRS since is characterizes by a very rapid deterioration of renal function. Eventually, most of the patients regain renal function, but it is unknown if this is due to the transplanted kidney, the recovery of native renal function, or both. The aim of this study is to evaluate if there is recovery of native renal function in patients with HRS following CKLT. 22 patients (16 men; 6 women) with history of HRS and status post CKLT were studied. Mercapto-acetyltriglycine-3 renograms in the anterior and posterior views with the three kidneys in the field of view were simultaneously acquired. The renograms were analyzed by creating regions of interest around the transplanted and native kidneys. Relative contribution to the renal function, clearance, and effective renal plasma flow for the transplanted and native kidneys were obtained. 1/22 (4.5%) patients presented with a very poor functioning transplanted kidney, in 15/22 (68%) cases the combined native renal function was markedly poorer than the transplanted renal function and in 6/22 (27%) native kidneys showed a contribution to the renal function similar to the transplanted kidney. In conclusion, our series show that around 32% of the HRS patients recovered their native renal function after CKLT. Identification of common factors that affect recovery of native renal function may help to avoid unnecessary renal transplants, significantly reducing morbidity and cost, while facilitating a reallocation of scarce donor resources.

Objective: To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent., Materials and Methods: Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach., Results: A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values <0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson's correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT., Conclusions: A simultaneous PET/MRI using both (68)Ga-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.

Positron emission tomography (PET) is currently the most advanced technique of metabolic imaging available for tumor diagnosis and follow-up. The aim of this study was to examine the versatility and accuracy of fluorodeoxyglucose (FDG) PET/computed tomography (CT) in the metastasis detection of renal cell carcinoma (RCC). We also compared our findings to other similar studies from the literature. This is the biggest study so far to examine the sensitivity and specificity of FDG PET/CT in the management of RCC. A retrospective review was carried out on all the FDG PET/CT studies done from January 1999 to January 2014 at our institution. Biopsy results were considered the gold standard. For our patients (n = 315) with biopsy results, FDG PET/CT studies exhibited 100% sensitivity, 100% specificity. Our results were better than results achieved by other studies. The use of FDG PET/CT in restaging and metastasis detection of RCC has many advantages, in addition to high accuracy. This imaging technique has great potential in influencing treatment decisions. We recommend the incorporation of FDG PET/CT in routine standard protocols for RCC.

Focal (18)F-fluorodeoxyglucose (FDG) colonic activity can be incidentally seen in positron emission tomography/computed tomography (PET/CT) scans. Its clinical significance is still unclear. The purpose of this study was to assess the significance of focal FDG activity in PET/CT scans by correlating the imaging findings to colonoscopy results, and come up with some guidelines for recommendation of follow-up colonoscopy. A total of 133 patients who underwent both (18)F-FDG PET/CT for different oncological indications and colonoscopy within 3 months were retrospectively studied. Imaging, colonoscopy and pathology results were analyzed. Of the 133 FDG-PET/CT scans, 109/133 (82%) did not show focal colonic FDG activity, and 24/133 (18%) did. Of the 109/133 PET/CTs without focal colonic FDG activity, 109/109 (100%) did not have evidence of colon cancer after colonoscopy and histology. Of the 24/133 PET/CTs with focal colonic FDG activity, 10/24 (42%) had pathologic confirmation of colon cancer and 14/24 (58%) did not have evidence of colon cancer after colonoscopy and histological analysis. Sensitivity was 10/10 (100%), specificity 109/123 (89%), positive predictive value (PPV) 10/24 (42%) and negative predictive value (NPV) 109/109 (100%). Incidental focal (18)FDG activity in PET/CT imaging shows a high sensitivity, specificity and NPV for malignancy, with a not so high PPV of 42%. Although some people would argue that a 42% chance of malignancy justifies colonoscopy, this maybe is not possible in all cases. However, the high sensitivity of the test does not allow these studies to be overlooked. We provide our recommendations as per when to send patients with focal FDG colonic activity to have further characterization with colonoscopy.

Background: The primary aim of this study was to examine if factors such as renal function, height, weight and age could affect the uptake of sodium fluoride-18 (NaF-18) by the normal bone. This is the first study to examine the possible factors that can influence NaF-18 uptake in the normal bone., Methods: A retrospective study was done on NaF-18 PET/CT bone scans from January 2010 to May 2012 at our institution. All NaF-18 PET/CT studies used the same clinical protocol. Our excluding criteria were patients with abnormal renal function and patients with past history of cancer and metabolic bone diseases. Spearman's correlation was used to analyze the data., Results: From our study (n = 11 patients), no correlation was found between SUVmax and serum creatinine and between SUVmax and age. However, significant correlations were found between SUVmax and height (cm) and between SUVmax and weight (kg) for thoracic 5, 7, 12 and lumbar 2 vertebral levels., Conclusion: Based on our findings, SUVmax values in NaF-18 PET/CT bone scans can vary depending on the patient's height, weight and bone region. This information can be helpful in diagnosing and monitoring bone pathologies and can help explain the clinical findings.

Objectives: Nonreal-time Positron Emission Tomography/Computed Tomography (PET/CT) biopsies that use the image co-registration of a prior PET with an intra-procedural CT have been reported. The aim of this study was to report the initial experience of performing real-time intra-procedural PET/CT-guided biopsies., Materials and Methods: All patients (n = 4) had a prior PET/CT examination of the concerning lesion and no significant CT correlate. On the day of the biopsy, 5 mCi of 18F-fluorodeoxyglucose (FDG) or NaF18 was intravenously injected. After 60 min of biodistribution of the molecular probe, PET/CT images were obtained in a limited one bed position over the region of the concerning lesion to be biopsied., Results: One patient had a mesenteric mass and the other three had bone lesions, one located in the rib and two in the iliac bone. The pathology report revealed that two lesions (50%) were malignant and two lesions (50%) were benign. The results of the biopsy changed management in all cases. There was 0% complication rate., Conclusions: No additional software or hardware is required to perform real-time intra-procedural PET/CT-guided biopsies. It can optimize the yield, especially in cases where there are no anatomical abnormalities. Real-time intra-procedural PET/CT biopsy may have benefits over conventional biopsy techniques in terms of accuracy.

Objectives: Cancer and metabolic bone diseases can alter the SUV. SUV values have never been measured from healthy skeletons in NaF18-PET/CT bone scans. The primary aim of this study was to measure the SUV values from normal skeletons in NaF18-PET/CT bone scans., Methods: A retrospective study was carried out involving NaF18- PET/CT bone scans that were done at our institution between January 2010 to May 2012. Our excluding criteria was patients with abnormal real function and patients with past history of cancer and metabolic bone diseases including but not limited to osteoporosis, osteopenia and Paget's disease. Eleven studies met all the criteria., Results: The average normal SUVmax values from 11 patients were: cervical vertebrae 6.84 (range 4.38-8.64), thoracic vertebrae 7.36 (range 6.99-7.66), lumbar vertebrae 7.27 (range 7.04-7.72), femoral head 2.22 (range 1.1-4.3), humeral head 1.82 (range 1.2-2.9), mid sternum 5.51 (range 2.6-8.1), parietal bone 1.71 (range 1.3-2.4)., Conclusion: According to our study, various skeletal sites have different normal SUV values. SUV values can be different between the normal bones and bones with tumor or metabolic bone disease. SUV can be used to quantify NaF-18 PET/CT studies. If the SUV values of the normal skeleton are known, they can be used in the characterization of bone lesions and in the assessment of treatment response to bone diseases.

We report a case of a 59-year-old woman with right ventricular metastasis of undifferentiated endometrial cancer. Cardiac metastasis from endometrial cancer is a very rare finding. The case demonstrates that undifferentiated endometrial cancer is capable of metastasizing, presumably through a hematogenous route, to unexpected distant organs. These unexpected sites should not be undermined in the restaging and surveillance of these patients.

Background and Purpose: From the literature, the prevalence of fluorodeoxyglucose (FDG) uptake in large artery atherosclerotic plaques shows great heterogeneity. We retrospectively reviewed 100 consecutive patients who underwent FDG-positron emission tomography-computed tomography (PET/CT) imaging of their whole body, to evaluate FDG uptake in the arterial wall., Materials and Methods: We retrospectively evaluated 100 whole-body PET-CT scans. The PET images coregistered with CT were reviewed for abnormal 18F-FDG uptake. The mean standard uptake value (SUV) was measured in regions of interest (ROIs). The prevalence of PET+ plaques was determined based on the qualitative PET review, used as the gold standard in a receiver-operating characteristic (ROC) curve analysis to determine an optimal threshold for the quantitative PET analysis., Results: The qualitative, visual assessment demonstrated FDG uptake in the arterial walls of 26 patients. A total of 85 slices exhibited FDG uptake within the arterial wall of 37 artery locations. 11, 17, and 2 patients exhibited FDG uptake within the wall of carotid arteries, of the aorta, and of the iliac arteries, respectively. Only 4 of the 26 patients had positive FDG uptake in more than one artery location. In terms of quantitative analysis, a threshold of 2.8 SUV was associated with a negative predictive value of 99.4% and a positive predictive value of 100% to predict qualitative PET+ plaques. A threshold of 1.8 SUV was associated with a negative predictive value of 100% and a positive predictive value of 99.4%. Area under the ROC curve was .839., Conclusion: The prevalence of PET uptake in arterial walls in a consecutive population of asymptomatic patients is low and usually confined to one type of artery, and its clinical relevance in terms of vulnerability to ischemic events remains to be determined., (Copyright © 2012 by the American Society of Neuroimaging.)

Cardiac single photon emission computed tomography (SPECT) cameras typically rotate too slowly around a patient to capture changes in the blood pool activity distribution and provide accurate kinetic parameters. A spatiotemporal iterative reconstruction method to overcome these limitations was investigated. Dynamic rest/stress (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT/CT was performed along with reference standard rest/stress dynamic positron emission tomography (PET/CT) (13)N-NH3 in five patients. The SPECT data were reconstructed using conventional and spatiotemporal iterative reconstruction methods. The spatiotemporal reconstruction yielded improved image quality, defined here as a statistically significant (p<0.01) 50% contrast enhancement. We did not observe a statistically significant difference between the correlations of the conventional and spatiotemporal SPECT myocardial uptake K 1 values with PET K 1 values (r=0.25, 0.88, respectively) (p<0.17). These results indicate the clinical feasibility of quantitative, dynamic SPECT/CT using (99m)Tc-MIBI and warrant further investigation. Spatiotemporal reconstruction clearly provides an advantage over a conventional reconstruction in computing K 1.