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Objective: [ 18 F]FDG imaging is an integral part of patient management in CAR-T-cell therapy for recurrent or therapy-refractory DLBCL. The calculation methods of predictive power of specific imaging parameters still remains elusive. With this retrospective study, we sought to evaluate the predictive power of the baseline metabolic parameters and tumor burden calculated with automated segmentation via different thresholding methods for early therapy failure and mortality risk in DLBCL patients., Materials and Methods: Eighteen adult patients were enrolled, who underwent CAR-T-cell therapy accompanied by at least one pretherapeutic and two posttherapeutic [ 18 F]FDG PET scans within 30 and 90 days between December 2018 and October 2023. We performed single-click automatic segmentation within VOIs in addition to extracting the SUV parameters to calculate the MTVs and TLGs by applying thresholds based on the concepts of a fixed absolute threshold with an SUV max > 4.0, a relative absolute threshold with an isocontour of > 40 % of the SUV max , a background threshold involving the addition of the liver SUV value and its 2 SD values, and only the liver SUV value., Results: For early therapy failure, baseline metabolic parameters such as the SUV max , SUV peak and SUV mean tended to have greater predictive power than did the baseline metabolic burden. However, the baseline metabolic burden was superior in the prediction of mortality risk regardless of the thresholding method used., Conclusion: This study revealed that automated delineation methods of metabolic tumor burden using different thresholds do not differ in outcome substantially. Therefore, the current clinical standard with a fixed absolute threshold value of SUV > 4.0 seems to be a feasible option., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BNB received travel support from Kite Gilead and Medac and speaker honoraria from Incyte. He has membership at GLA and EBMT and an advisory role at Kite Gilead. GK received honoraria from MSD, Pfizer, Amgen, Novartis, Gilead, BMSCelgene, Abbvie, Biotest, Takeda, Eurocept, Jazz, Medac, and Eurocept. He received lecture fees from MSD, Pfizer, Amgen, Novartis, Gilead, BMSCelgene, Abbvie, Biotest, Takeda, Eurocept, and Jazz. The other authors declare no conflicts of interest regarding this manuscript. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Competing Interests: Declarations. Ethical approval: This study was conducted in accordance with the principles of the Declaration of Helsinki. Approval was granted by the institutional review board of Osaka University Hospital (approval number: 239012-A). Consent to participate and publish: Written informed consent was obtained from the patient. Conflict of interest: FLG is an advisor at ABX Radiopharmaceuticals, SOFIE Biosciences, Telix Pharma, and Alpha Fusion. FLG holds shares in a consultancy group for iTheranostics. The other authors declare no potential conflicts of interest relevant to this study.

Background: Risk-adjusted screening for prostate cancer (PCa) aims to reduce harms by less frequent retesting, especially in men at a low risk of PCa. Definitions of low risk are based mainly on studies in men starting screening at age 55-60 yr., Objective: To identify men at age 45 yr with a low risk of PCa., Design, Setting, and Participants: A population-based, risk-adjusted PCa screening trial was conducted in Germany using baseline prostate-specific antigen (PSA) starting in young men (PROBASE)., Intervention: PSA measurements starting at the age of 45 yr., Outcome Measurements and Statistical Analysis: The incidence of PCa within 5 yr was assessed in men with screen-negative baseline PSA <1.5 ng/ml compared with those with PSA 1.5-≤3.0 ng/ml., Results and Limitations: Of 23301 men who received a first PSA test at age 45 yr, 0.79% had a screen-positive PSA value of ≥3 ng/ml. Among the 89% of men who had a screen-negative baseline PSA value of <1.5 ng/ml, only 0.45% received a positive PSA test ≥3 ng/ml upon retesting after 5 yr. By contrast, for those with a screen-negative baseline PSA value of 1.5-3 ng/ml, 13% surpassed 3 ng/ml upon biennial testing within the next 4 yr. The incidence of PCa in subsequent screening rounds increased with increasing baseline PSA levels, from 0.13 per 1000 person-years for men with initial PSA level of <1.5 ng/ml to 8.0 per 1000 person-years for those with PSA levels of 1.5-3.0 ng/ml. A limitation is a follow-up time of only 5 yr, so far., Conclusions: Men with baseline PSA <1.5 ng/ml at age 45 yr are at a very low risk of PCa over the next 5 yr., Patient Summary: The PROBASE study showed that men with baseline prostate-specific antigen (PSA) <1.5 ng/ml at age 45 yr have a very low prostate cancer detection rate over 5 yr and do not need PSA retesting during this time., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Novel nuclear medicine therapeutics are being developed by labeling medium-molecular-weight compounds with short-lived alpha-emitting radionuclides. Fibroblast activation protein α (FAPα) is recognized as a highly useful molecular target, and its inhibitor, FAPI, is a compound capable of theranostics , both therapeutic and diagnostic, for cancer treatment. In this study, we compared the functions of two compounds that target FAPα: 211 At-FAPI1 and 211 At-FAPI2. First, in vitro screening procedures are generally accepted because of the low endogenous expression of FAPα. We suggest the usefulness of this 3D culture system for in vitro screening. Second, when FAPIs are used therapeutically, the expected therapeutic effects are often not achieved. Therefore, we compared the accumulation and excretion in tumor tissues and the anti-tumor effects based on the length of the linker in the compounds. The compounds were rapidly labeled using the Shirakami reaction . Doubling the linker length increased tumor retention. Additionally, the excretion pathway was altered, suggesting a potential reduction in toxicity. Although no significant differences were observed in the anti-tumor effects of 211 At-FAPI1 and 211 At-FAPI2, it was confirmed that the linker length affects the biological half-life.

Prostate adenocarcinoma metastasis to brain has been reported to occur only up to 0.6% of patients and these are mostly diagnosed in autopsy series. In the setting of biochemical recurrence of prostate cancer, a suspected PSMA-avid (prostate-specific membrane antigen) lesion in the brain is still strongly suggestive of an intracranial metastasis of prostate cancer. This needs, however, a thoroughly recurrency work-up due to other potentially PSMA-avid cranial lesions, as PSMA initially was developed for the imaging of primary CNS tumours. We report of a challenging clinical case of a 71-year-old-patient with a strongly PSMA-avid lesion at the skull base. Given the medical history of a meningioma at the skull base, the further diagnostic work-up with MRI could still not rule out a malignancy, so that the patient needed to undergo a surgical excision of the tumour mass. The histological and immunohistochemical examinations revealed a relapsed CNS WHO grade 1 meningioma. From the aspect of molecular imaging and critical analysis of regular clinical care in a third-level university hospital, we consider this result very intriguing. Hence, we analyse the decision-making process and clinical course of this case in the light of molecular imaging findings., Competing Interests: F.L.G. has patent application for [18F]PSMA-1007 and is an advisor at ABX, Telix, Alpha Fusion, and SOFIE Biosciences. The other authors declare no conflict of interest regarding this manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Interstitial lung diseases (ILD) encompass a wide range of disorders characterized by alveolar inflammation and fibrotic tissue remodeling, marked by significant morbidity and mortality. Systemic sclerosis (SSc), among other connective tissue diseases, is a frequent cause of ILD. Assessment of pulmonary fibrosis is frequently constrained by the delayed manifestations of profibrotic activation of fibroblasts, which results in late macroscopic alterations detectable by standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans. 68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI [fibroblast activation protein inhibitor]) are novel radionuclides used in the selective positron emission tomography/computed tomography (PET/CT) detection of profibrotic fibroblasts, a key player in fibrotic tissue remodeling. Application of 68Ga-FAPI in different target organs undergoing fibrosis, such as lung and heart, highlights its efficacy in detecting ongoing fibrotic processes, since FAPI tracer uptake has been correlated with clinical disease progression markers in SSc-ILD. This feature could enable physicians to detect subclinical fibrotic activity and tailor an individualised therapy plan on a case by case basis. The use of 68Ga-FAPI in ILD and other fibrotic conditions may emerge as a novel tool in future clinical practice for both activity monitoring and treatment optimisation. Other tracers tested in ILD of different etiologies have shown promising results and may in future also be considered for potential application in SSc-ILD., (© 2024 Mihai Tudor Albu, Alexandru-Emil Matei, Jörg H. W. Distler, Frederik L. Giesel, Yuriko Mori, published by De Gruyter on behalf of NCRC-DID.)

Purpose: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection., Procedures: Seventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [ 18 F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard., Results: Nine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm 3 , and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555-0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571-0.964), respectively., Conclusions: Volumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [ 18 F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection., (© 2024. The Author(s).)

Purpose: For understanding the neurochemical mechanism of neuropsychiatric conditions associated with cognitive deficits it is of major relevance to elucidate the influence of serotonin (5-HT) agonists and antagonists on memory function as well dopamine (DA) and 5-HT release and metabolism. In the present study, we assessed the effects of the 5-HT 2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and the 5-HT 2A receptor altanserin (ALT) on object and place recognition memory and cerebral neurotransmitters and metabolites in the rat., Methods: Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography., Results: DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP., Conclusions: DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest (either financial or non-financial)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Investigate the feasibility of detecting early treatment-induced tumor tissue changes in patients with advanced lung adenocarcinoma using diffusion-weighted MRI-derived radiomics features., Methods: This prospective observational study included 144 patients receiving either tyrosine kinase inhibitors (TKI, n = 64) or platinum-based chemotherapy (PBC, n = 80) for the treatment of pulmonary adenocarcinoma. Patients underwent diffusion-weighted MRI the day prior to therapy (baseline, all patients), as well as either + 1 (PBC) or + 7 and + 14 (TKI) days after treatment initiation. One hundred ninety-seven radiomics features were extracted from manually delineated tumor volumes. Feature changes over time were analyzed for correlation with treatment response (TR) according to CT-derived RECIST after 2 months and progression-free survival (PFS)., Results: Out of 14 selected delta-radiomics features, 6 showed significant correlations with PFS or TR. Most significant correlations were found after 14 days. Features quantifying ROI heterogeneity, such as short-run emphasis (p = 0.04 (pfs) /0.005 (tr) ), gradient short-run emphasis (p = 0.06 (pfs) /0.01 (tr) ), and zone percentage (p = 0.02 (pfs) /0.01 (tr) ) increased in patients with overall better TR whereas patients with worse overall response showed an increase in features quantifying ROI homogeneity, such as normalized inverse difference (p = 0.01 (pfs) /0.04 (tr) ). Clustering of these features allows stratification of patients into groups of longer and shorter survival., Conclusion: Two weeks after initiation of treatment, diffusion MRI of lung adenocarcinoma reveals quantifiable tissue-level insights that correlate well with future treatment (non-)response. Diffusion MRI-derived radiomics thus shows promise as an early, radiation-free decision-support to predict efficacy and potentially alter the treatment course early., Critical Relevance Statement: Delta-Radiomics texture features derived from diffusion-weighted MRI of lung adenocarcinoma, acquired as early as 2 weeks after initiation of treatment, are significantly correlated with RECIST TR and PFS as obtained through later morphological imaging., Key Points: Morphological imaging takes time to detect TR in lung cancer, diffusion-weighted MRI might identify response earlier. Several radiomics features are significantly correlated with TR and PFS. Radiomics of diffusion-weighted MRI may facilitate patient stratification and management., (© 2024. The Author(s).)

Fibroblast activation protein (FAP) is mainly found on the surface of activated fibroblasts but is not expressed on the surface of inactive fibroblasts. Selective FAP inhibitors (FAPI), which are coupled to a radioactive tracer, can be used to quantify profibrotic and proinflammatory fibroblasts in patients using FAPI positron emission tomography (PET) computed tomography (CT). Following initial applications in neoplastic diseases, FAPI-PET/CT is also increasingly being applied in rheumatological diseases. The first studies have shown that in patients with systemic sclerosis (SSc) FAPI accumulates in actively fibrotically remodeled pulmonary and myocardial areas, that a high FAPI accumulation is associated with the risk of short-term progression and that this accumulation in the lungs regresses after successful treatment. In cases of immunoglobulin 4 (IgG4)-associated diseases (IgG4 rheumatic disease, RD), the FAPI signal correlates with the histological accumulation of activated fibroblasts and a poorer response to treatment to inhibit inflammation. Fibroblasts in chronically inflamed tissue, such as patients with inflammatory joint diseases, vasculitis or myositis, also express FAP and can be quantified by FAPI-PET/CT. The treatment-induced change of the phenotype from a destructive IL-6+/MMP3+THY1+ fibroblast subtype to an inflammation inhibiting CD200+DKK3+ subtype can be mechanistically demonstrated using FAPI-PET/CT. These studies provide indications that FAPI-PET/CT enables quantification of the tissue response in patients with fibrosing and chronic inflammatory diseases and can be used for patient stratification; however, further studies are essential for validation of the use of FAPI-PET/CT as a molecular imaging marker., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Competing Interests: All authors declare that they have no conflicts of interest regarding this article. Disclosures: Frederik L. Giesel is a consultant at ABX, SOFIE Biosciences and Telix and holds small patent interests in F18-PSMA-1007 and FAP ligands.

Purpose: This study aimed to evaluate the prognostic potential of pre-therapeutic [18F]FDG-PET/CT variables regarding prediction of progression-free survival (PFS) and overall survival (OS) in NSCLC-patients., Method: NSCLC-patients who underwent pre-therapeutic [18F]FDG-PET/CT were retrospectively analyzed. The following imaging features were collected from the primary tumor: tumor size, tumor density, central necrosis, spicules and SUVmax. For standardization, an indexSUVmax was calculated (SUVmax primary tumor/SUVmax liver). Descriptive statistics and correlations of survival time analyses for PFS and OS were calculated using the Kaplan-Meier method and Cox regression including a hazard ratio (HR). A value of p < 0.05 was set as statistically significant. The 95%-confidence intervals (CI) were calculated. The median follow-up time was 63 (IQR 27-106) months., Results: This study included a total of 82 patients (25 women, 57 men; mean age: 66 ± 9 years). IndexSUVmax (PFS: HR = 1.0, CI: 1.0-1.1, p = 0.49; OS: HR = 1.0, CI: 0.9-1.2, p = 0.41), tumor size (PFS: HR = 1.0, CI: 0.9-1.0, p = 0.08; OS: HR = 1.0, CI: 0.9-1.0, p = 0.07), tumor density (PFS: HR = 0.9, CI: 0.6-1.4, p = 0.73; OS: HR = 0.3; CI: 0.1-1.1; p = 0.07), central necrosis (PFS: HR = 1.0, CI: 0.6-1.8, p = 0.98; OS: HR = 0.6, CI: 0.2-1.9, p = 0.40) and spicules (PFS: HR = 1.0, CI: 0.6-1.9, p = 0.91; OS: HR = 1.3, CI: 0.4-3.7, p = 0.65) did not significantly affect PFS and OS in the study population. An optimal threshold value for the indexSUVmax was determined by ROC analysis and Youden's index. There was no significant difference in PFS with an indexSUVmax-threshold of 3.8 (13 vs. 27 months; p = 0.45) and in OS with an indexSUVmax-threshold of 4.0 (113 vs. 106 months; p = 0.40)., Conclusions: SUVmax and morphologic parameters from pre-therapeutic [18F]FDG-PET/CT were not able to predict PFS and OS in NSCLC-patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Peters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Both dopamine (DA) and serotonin (5-HT) play key roles in numerous functions including motor control, stress response and learning. So far, there is scarce or conflicting evidence about the effects of 5-HT1A and 5-HT2A receptor (R) agonists and antagonists on recognition memory in the rat. This also holds for their effect on cerebral DA as well as 5-HT release. In the present study, we assessed the effects of the 5-HT 1A R agonist 8-OH-DPAT and antagonist WAY100,635 and the 5-HT 2A R agonist DOI and antagonist altanserin (ALT) on rat behaviors. Moreover, we investigated their impact on monoamine efflux by measuring monoamine transporter binding in various regions of the rat brain. After injection of either 8-OH-DPAT (3 mg/kg), WAY100,635 (0.4 mg/kg), DOI (0.1 mg/kg), ALT (1 mg/kg) or the respective vehicle (saline, DMSO), rats underwent an object and place recognition memory test in the open field. Upon the assessment of object exploration, motor/exploratory parameters and feces excretion, rats were administered the monoamine transporter radioligand N-o-fluoropropyl-2b-carbomethoxy-3b-(4-[ 123 I]iodophenyl)-nortropane ([ 123 I]-FP-CIT; 8.9 ± 2.6 MBq) into the tail vein. Regional radioactivity accumulations in the rat brain were determined post mortem. Compared vehicle, administration of 8-OH-DPAT impaired memory for place, decreased rearing behavior, and increased ambulation as well as head-shoulder movements. DOI administration led to a reduction in rearing behavior but an increase in head-shoulder motility relative to vehicle. Feces excretion was diminished after ALT relative to vehicle. Dopamine transporter (DAT) binding was increased in the caudateputamen (CP), but decreased in the nucleus accumbens (NAC) after 8-OH-DPAT relative to vehicle. Moreover, DAT binding was decreased in the NAC after ALT relative to vehicle. Findings indicate that 5-HT 1A R inhibition and 5-HT 2A R activation may impair memory for place. Furthermore, results imply associations not only between recognition memory, motor/exploratory behavior and emotionality but also between the respective parameters and the levels of available DA in CP and NAC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest (either financial or non-financial)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The advancement of theranostics, which combines therapeutic and diagnostic capabilities in oncology, has significantly impacted cancer management. This review explores fibroblast activation protein (FAP) expression in the tumor microenvironment (TME) and its association with various malignancies, highlighting its potential as a theranostic marker for PET/CT imaging using FAP-targeted tracers and for FAP-targeted radiopharmaceutical therapy. We examine the development and clinical applications of FAP inhibitors (FAPIs) and peptides, providing insights into their diagnostic accuracy, initial therapeutic efficacy, and clinical impact across diverse cancer types, as well as the synthesis of novel FAP-targeted ligands. This review aims to showcase the promising outcomes and challenges in integrating FAP-targeted approaches into cancer management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Frederik L. Giesel is a FAPI co-inventor and is an advisor at Telix Pharma, SOFIE, ABX, and Alpha Fusion and receives royalties from iTheranostics and SOFIE Biosciences. Richard P. Baum is an advisor to 3B Pharmaceuticals (Berlin, Germany), ITM, Full Life Technologies, Sinotau, Jiangsu Huayi Technology, and Telix Pharmaceuticals, and cofounder of RadioVaxx GmbH., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Fibroblast activation protein (FAP) is a serine integral membrane protease, the expression of which has been confirmed in various cancer types. Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal fibroblastic neoplasms. We present a case of 18 F-labeled FAP inhibitor ([ 18 F]FAPI-74) PET imaging and its correlation with histological FAP expression and review an SFTP series at our institution in relation to the extent of FAP expression., Methods: This retrospective study included 13 patients who underwent surgery between March 2011 and December 2022 at our institute. One of the patients also underwent [ 18 F]FAPI-74 PET imaging. We semi-quantitatively evaluated FAP expression in SFTPs using immunohistochemical staining and H-scores., Results: Nine of the 13 patients were male, with a median age of 64 years (range, 28-79 years). The median tumor size was 6.6 cm (1.1, 16 cm). In the pathological findings, expression levels of Ki67 were 1-5% in 12 of 13 cases. Furthermore, FAP expression was observed in all patients, and the median H-score was 160 (range, 10-280). The H-score of FAP expression in two of the 13 patients was low (10 in both), and that in two of the 13 patients was high (240 and 280). The SUVmax value of [ 18 F]FAPI-74 PET was 3.57 in a patient in whom the H-score of FAP expression was 180., Conclusions: SFTPs expressed FAP to varying degrees in different patients and the [ 18 F]FAPI-74 PET results in one patient reflected FAP expression in the tumor tissue., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Toru Kimura reports financial support was provided by Japan Society for the Promotion of Science. Toru Kimura reports financial support was provided by The Japan Lung Cancer Society. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The aim of this work is to evaluate our clinical real-world data obtained with 225 Ac-PSMA-617 (AcPSMA), which were acquired under compassionate care regulations in patients with advanced-stage prostate cancer. The objective parameters that could be derived from this evaluation are compared with previous literature about AcPSMA and 177 Lu-PSMA-617 (LuPSMA). Methods: The medical files of all patients who had received AcPSMA on an individual patient basis at the Heidelberg University Hospital since January 2014 were analyzed retrospectively. Previously published patients were excluded. The remaining patients were tailored into 2 subgroups with different treatment strategies: group 1 received AcPSMA as a deescalated monotherapy, and group 2 received LuPSMA plus AcPSMA as a cocktail regimen. Baseline characteristics, serum prostate-specific antigen (PSA) response, and overall survival were compared with the most appropriate historical controls. Results: Of 287 patients treated, 54 were excluded because of previous publication and 233 were evaluated, 104 of whom received AcPSMA monotherapy (median, 6 MBq). In this group, 55 patients (53%) presented with a best PSA response of at least 50%. The other 129 patients received a cocktail therapy of AcPSMA (median, 4 MBq) plus LuPSMA (4 GBq). In this group, a best PSA response of at least 50% was observed in 74 patients (57%). The median overall survival in the monogroup was 9 mo and in the cocktail group was 15 mo. If adjusted for prognostic baseline characteristics, the efficacy of both regimens was not significantly different. Conclusion: Deescalated treatment activities of AcPSMA or AcPSMA and LuPSMA cocktail regimens present better tolerability with regard to xerostomia than previous regimens of at least 100 kBq/kg while retaining high antitumor activity in poor-prognosis prostate cancer patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Astatine ( 211 At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211 At-labeled prostate-specific membrane antigen (PSMA) compound ([ 211 At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [ 211 At]PSMA-5 was administered to both normal male ICR mice ( n = 85) and cynomolgus monkeys ( n = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( n = 10 per group) and 14 days ( n = 5 per group). Monkeys were observed 24 h post-administration of [ 211 At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [ 211 At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of 211 At using a cyclotron supports its applicability for clinical use.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. 68 Ga-labeled FAP ligands exhibited highly promising results due to the crucial role of activated fibroblasts in fibrosis imaging of the lung. However, 18 F-labeled FAP ligands might provide qualitatively much higher imaging results with accompanying economic benefits due to large-scale production. Thus, we sought to investigate the potential of [ 18 F]FAPI-74 prospectively in a small patient cohort., Methods: Eight patients underwent both [ 18 F]FAPI-74-PET/CT and HRCT scans and were then compared with a control group without any fibrosing pulmonary disease. The tracer uptake of fibrotic lung areas was analyzed in synopsis with radiological and clinical parameters., Results: We observed a positive correlation between the fibrotic active volume, the Hounsfield scale, as well as the vital and diffusing capacity of the lung., Conclusion: The initial results confirm our assumption that [ 18 F]FAPI-74 offers a viable non-invasive assessment method for pulmonary fibrotic changes in patients with IPF., (© 2023. The Author(s).)

Purpose: [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [ 18 F]FDG PET/CT. This study aimed to evaluate [ 18 F]PSMA-1007 and [ 18 F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively., Method: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [ 18 F]PSMA-1007 and [ 18 F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed., Results: All 42 index tumours were detected on [ 18 F]PSMA-1007 PET/CT, whereas only 15 were detected on [ 18 F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUV max for [ 18 F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [ 18 F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [ 18 F]PSMA-1007 uptake than tumours without [ 18 F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [ 18 F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [ 18 F]FDG negative tumours but in 53.3% (8/15) of patients with [ 18 F]FDG positive tumours (p = 0.013)., Conclusions: [ 18 F]PSMA-1007 PET/CT was superior to [ 18 F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [ 18 F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [ 177 Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177 Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99m Tc or therapeutically with 188 Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [ 99m Tc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking., Procedures: Two cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [ 99m Tc]Tc-EDDA/HYNIC-iPSMA or [ 99m Tc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden)., Results: The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [ 99m Tc]Tc-PSMA-GCK01 compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [ 99m Tc]Tc-PSMA-GCK01 vs. median 9.11 [ 99m Tc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [ 99m Tc]Tc-PSMA-GCK01 (0.83) compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands., Conclusions: The novel theranostic tracer [ 99m Tc]Tc/[ 188 Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization., (© 2023. The Author(s).)

Background: Magnetic resonance imaging (MRI) has been suggested as a tool for guiding biopsy recommendations in prostate cancer (PC) screening., Objective: To determine the performance of multiparametric MRI (mpMRI) in young men at age 45 yr who participated in a PC screening trial (PROBASE) on the basis of baseline prostate-specific antigen (PSA)., Design, Setting, and Participants: Participants with confirmed PSA ≥3 ng/ml were offered mpMRI followed by MRI/transrectal ultrasound fusion biopsy (FBx) with targeted and systematic cores. mpMRI scans from the first screening round for men randomised to an immediate PSA test in PROBASE were evaluated by local readers and then by two reference radiologists (experience >10 000 prostate MRI examinations) blinded to the histopathology. The PROBASE trial is registered as ISRCTN37591328 OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The local and reference Prostate Imaging-Data and Reporting System (PI-RADS) scores were compared, and the sensitivity, negative predictive value (NPV), and accuracy were calculated for both readings for different cutoffs (PI-RADS 3 vs 4)., Results and Limitations: Of 186 participants, 114 underwent mpMRI and FBx. PC was detected in 47 (41%), of whom 33 (29%) had clinically significant PC (csPC; International Society of Urological Pathology grade group ≥2). Interobserver reliability between local and reference PI-RADS scores was moderate (k = 0.41). At a cutoff of PI-RADS 4, reference reading showed better performance for csPC detection (sensitivity 79%, NPV 91%, accuracy of 85%) than local reading (sensitivity 55%, NPV 80%, accuracy 68%). Reference reading did not miss any PC cases for a cutoff of PI-RADS <3. If PI-RADS ≥4 were to be used as a biopsy cutoff, mpMRI would reduce negative biopsies by 68% and avoid detection of nonsignificant PC in 71% of cases., Conclusions: Prostate MRI in a young screening population is difficult to read. The MRI accuracy of for csPC detection is highly dependent on reader experience, and double reading might be advisable. More data are needed before MRI is included in PC screening for men at age 45 yr., Patient Summary: Measurement of prostate specific antigen (PSA) is an effective screening test for early detection of prostate cancer (PC) and can reduce PC-specific deaths, but it can also lead to unnecessary biopsies and treatment. Magnetic resonance imaging (MRI) after a positive PSA test has been proposed as a way to reduce the number of biopsies, with biopsy only recommended for men with suspicious MRI findings. Our results indicate that MRI accuracy is moderate for men aged 45 years but can be increased by a second reading of the images by expert radiologists. For broad application of MRI in routine screening, double reading may be advisable., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Currently, targeted alpha therapy (TAT) is a new therapy involving the administration of a therapeutic drug that combines a substance of α-emitting nuclides that kill cancer cells and a drug that selectively accumulates in cancer cells. It is known to be effective against cancers that are difficult to treat with existing methods, such as cancer cells that are widely spread throughout the whole body, and there are high expectations for its early clinical implementation. The nuclides for TAT, including 149 Tb, 211 At, 212/213 Bi, 212 Pb (for 212 Bi), 223 Ra, 225 Ac, 226/227 Th, and 230 U, are known. However, some nuclides encounter problems with labeling methods and lack sufficient preclinical and clinical data. We labeled the compounds targeting prostate specific membrane antigen (PSMA) with 211 At and 225 Ac. PSMA is a molecule that has attracted attention as a theranostic target for prostate cancer, and several targeted radioligands have already shown therapeutic effects in patients. The results showed that 211 At, which has a much shorter half-life, is no less cytotoxic than 225 Ac. In 211 At labeling, our group has also developed an original method ( Shirakami Reaction ). We have succeeded in obtaining a highly purified labeled product in a short timeframe using this method.

Background: Annual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial., Objective: To determine DRE diagnostic performance in a screening trial., Design, Setting, and Participants: This analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa., Intervention: (1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen-driven biopsies (N = 578)., Outcome Measurements and Statistical Analysis: (1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome at the time of a prostate biopsy were evaluated., Results and Limitations: (1) A prospective analysis of 57 men with suspicious DRE at age 45 revealed three PCa. Detection rate by DRE was 0.05% (three of 6537) as compared with a four-fold higher rate by PSA screening (48 of 23 301, 0.21%). The true-positive detection rate by DRE relative to screening by PSA was 0.22 (95% confidence interval [CI] = [0.07-0.72]) and the false-positive detection rate by DRE was 2.2 (95% CI = [1.50-3.17]). (2) Among PSA-screen-detected PCa cases, 86% had unsuspicious DRE (sensitivity relative to PSA was 14%), with the majority of these tumors (86%) located in the potentially accessible zones of the prostate as seen by magnetic resonance imaging., Conclusions: The performance of stand-alone DRE to screen for PCa is poor. DRE should not be recommended as a PCa screening test in young men. Furthermore, DRE does not improve the detection of PSA-screen-detected PCa., Patient Summary: Our report demonstrated the poor diagnostic performance of digital rectal examination in the screening for prostate cancer in young men., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Since the development of fibroblast activation protein-targeted radiopharmaceuticals, 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT has been found to be suitable for detecting primary and metastatic lesions in many types of tumors. However, there is currently a lack of reliable data regarding the clinical impact of this family of probes. To address this gap, the present study aimed to analyze the clinical impact of 68 Ga-FAPI PET/CT by examining a large cohort of patients with various tumors. Methods: In total, 226 patients (137 male and 89 female) were included in this retrospective analysis. Pancreatic cancer and head and neck cancers were the most common tumor types in this cohort. TNM stage and oncologic management were initially determined with gold standard imaging, and these results were compared with 68 Ga-FAPI PET/CT. Changes were classified as major and minor. Results: For 42% of all patients, TNM stage was changed by 68 Ga-FAPI PET/CT results. Most of these changes resulted in upstaging. A change in clinical management occurred in 117 of 226 patients. Although a major change in management occurred in only 12% of patients, there was a significant improvement in the ability to accurately plan radiation therapy. In general, the highest clinical impact of 68 Ga-FAPI PET/CT imaging was found in patients with lung cancer, pancreatic cancer, and head and neck tumors. Conclusion: 68 Ga-FAPI PET/CT is a promising imaging probe that has a significant impact on TNM stage and clinical management. 68 Ga-FAPI PET/CT promises to be a crucial new technology that will improve on conventional radiologic imaging methods such as contrast-enhanced CT and contrast-enhanced MRI typically acquired for cancer staging., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

In the present studies, we assessed the effect of the 5-HT 1A receptor (R) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on motor and exploratory behaviors, object and place recognition and dopamine transporter (DAT) and serotonin transporter (SERT) binding in the rat brain. In Experiment I, motor/exploratory behaviors were assessed in an open field after injection of either 8-OH-DPAT (0.1 and 3 mg/kg) or vehicle for 30 min without previous habituation to the open field. In Experiment II, rats underwent a 5-min exploration trial in an open field with two identical objects. After injection of either 8-OH-DPAT (0.1 and 3 mg/kg) or vehicle, rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Subsequently, N-o-fluoropropyl-2b-carbomethoxy-3b-(4-[ 123 I]iodophenyl)-nortropane ([ 123 I]FP-CIT; 11 ± 4 MBq) was injected into the tail vein. Regional radioactivity accumulations were determined post mortem with a well counter. In both experiments, 8-OH-DPAT dose-dependently increased ambulation and exploratory head-shoulder motility, whereas rearing was dose-dependently decreased. In the test rial of Experiment II, there were no effects of 8-OH-DPAT on overall activity, sitting and grooming. 8-OH-DPAT dose-dependently impaired recognition of object and place. 8-OH-DPAT (3 mg/kg) increased DAT binding in the dorsal striatum relative to both vehicle and 0.1 mg/kg 8-OH-DPAT. Furthermore, in the ventral striatum, DAT binding was decreased after 3 mg/kg 8-OH-DPAT relative to vehicle. Findings indicate that motor/exploratory behaviors, memory for object and place and regional dopamine function may be modulated by the 5-HT 1A R. Since, after 8-OH-DPAT, rats exhibited more horizontal and less (exploratory) vertical motor activity, while overall activity was not different between groups, it may be inferred, that the observed impairment of object recognition was not related to a decrease of motor activity as such, but to a decrease of intrinsic motivation, attention and/or awareness, which are relevant accessories of learning. Furthermore, the present findings on 8-OH-DPAT action indicate associations not only between motor/exploratory behavior and the recognition of object and place but also between the respective parameters and the levels of available DA in dorsal and ventral striatum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Positron emission tomography with 68 Gallium ( 68 Ga) labeled inhibitors of fibroblast activation protein ( 68 Ga-FAPI-PET) is a promising imaging technique for patients with recurrent pancreatic ductal adenocarcinomas (PDAC). To date, it is not clear if different acquisition timepoints for 68 Ga-FAPI-PET may result in comparable imaging information and if repetitive 68 Ga-FAPI-PET imaging may add diagnostic value to single timepoint acquisition for recurrent PDAC. Here we analyzed retrospectively early (20 min p.i.) and late (60 min p.i.) 68 Ga-FAPI-PET imaging using FAPI-46 of 33 patients with possible recurrence of PDAC concerning detection rates and uptake over time of local recurrences, metastases, inflammatory lesions of the pancreas, cholestatic lesions of the liver and reactive tissue. 33 patients with histologically confirmed PDAC after complete or partial resection of the pancreas and possible recurrence were examined by 68 Ga-FAPI-46-PET acquired 20- and 60-min post injection (p.i.) of the radiotracer. FAPI-positive lesions were classified as local recurrences, metastases, inflammatory lesions of the pancreas (ILP), cholestatic lesions of the liver and reactive tissue based on histology, PET- and CT-morphology and clinical information. Lesions were contoured, and standardized uptake values (SUVmax and SUVmean) and target-to-background ratios (TBR) were analyzed for both acquisition timepoints. In total, 152 FAPI-positive lesions (22 local relapses, 47 metastases, 26 inflammatory lesions of the pancreas, 28 reactive tissues, and 29 cholestatic lesions) were detected. Detection rates for the early and late acquisition of 68 Ga-FAPI-46-PET were almost identical except cholestatic lesions, which showed a higher detection rate at early imaging. SUV parameters and TBRs of ILP significantly decreased over time. Cholestatic lesions showed a tendency towards decreasing uptake. All other types of lesions showed relatively stable uptake over time. Early and late acquisition of 68 Ga-FAPI-PET results in comparable imaging information in patients with possible recurrence of PDAC. Two timepoint imaging offers additional diagnostic potential concerning differential diagnoses., (© 2023. Springer Nature Limited.)

Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1α). [ 68 Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [ 68 Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1α expression. The [ 68 Ga]Ga-FAPI PET/CT scans of women with cancer of the cervix were reviewed and the maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. Correlation analysis was performed between PET-derived parameters and immunohistochemical staining as well as between PET-derived parameters and the presence of metastasis. Ten women were included. All patients demonstrated tracer uptake in the primary site or region of the primary. All patients had lymph node metastases while only six patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI-TV was 18.89, 6.88, and 195.66 cm 3 , respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1α expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1α (r=0.80;p=0.017). The presence of skeletal metastasis was correlated to the HIF-1⍺ staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax.

The 18 F-labeled fibroblast activation protein inhibitor (FAPI) [ 18 F]FAPI-74 has the benefit of a higher synthetic yield and better image resolution than 68 Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [ 18 F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer ( n = 7), breast cancer ( n = 5), gastric cancer ( n = 5), pancreatic cancer ( n = 3), other cancers ( n = 5), and benign tumors ( n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [ 18 F]FAPI-74 PET scanning was performed 60 min after the intravenous injection of [ 18 F]FAPI-74 (240 ± 31 MBq). The [ 18 F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors ( n = 21) and nonmalignant lesions ( n = 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [ 18 F]FAPI-74 PET were also compared with those on [ 18 F]FDG PET for available patients ( n = 19). Results: [ 18 F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUV max , 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [ 18 F]FAPI-74 PET also showed significantly higher uptake than [ 18 F]FDG PET (median SUV max , 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [ P = 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [ P = 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [ P = 0.046], respectively). In 6 patients, [ 18 F]FAPI-74 PET detected more metastatic lesions than [ 18 F]FDG PET. Conclusion: [ 18 F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [ 18 F]FDG PET. [ 18 F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18 F-labeled FAPI ligand might serve a higher demand in clinical care in the future., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18 F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18 F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18 F-FDG PET/MRI. 18 F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI ( p < 0.0001 and p = 0.0005). Furthermore, 18 F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18 F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions: 18 F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Prostate-specific membrane antigen (PSMA) theranostics have been introduced with 68 Ga and 177 Lu, the most used radionuclides. However, 188 Re is a well-known generator-based therapeutic nuclide that completes a theranostic tandem with 99m Tc and may offer an interesting alternative to the currently used radionuclides. In the present work, we aimed at the development of a PSMA-targeted 99m Tc/ 188 Re theranostic tandem. Methods: The ligand HYNIC-iPSMA was chosen as the lead structure. Its HYNIC chelator has limitations for 188 Re labeling and was replaced by mercaptoacetyltriserine to obtain PSMA-GCK01, a precursor for stable 99m Tc and 188 Re labeling. 99m Tc-PSMA-GCK01 was used for in vitro evaluation of the ligand and comparison with 99m Tc-EDDA/HYNIC-iPSMA. Planar imaging using 99m Tc-PSMA-GCK01 and organ biodistribution with 188 Re-PSMA-GCK01 were performed using LNCaP tumor-bearing mice. Finally, the theranostic tandem was applied for imaging and therapy in 3 prostate cancer patients in compassionate care. Results: Efficient radiolabeling of PSMA-GCK01 with both radionuclides was demonstrated. Cell-based assays with 99m Tc-PSMA-GCK01 versus 99m Tc-EDDA/HYNIC-iPSMA revealed comparable uptake characteristics. Planar imaging and organ distribution revealed good tumor uptake of both 99m Tc-PSMA-GCK01 and 188 Re-PSMA-GCK01 at 1 and 3 h after injection, with low uptake in nontarget organs. In patients, similar distribution patterns were observed for 99m Tc-PSMA-GCK01 and 188 Re-PSMA-GCK01 and in comparison with 177 Lu-PSMA-617. Conclusion: The ligand PSMA-GCK01 labels stably with 99m Tc and 188 Re, both generator-based radionuclides, and thus provides access to on-demand labeling at reasonable costs. Preclinical evaluation of the compounds revealed favorable characteristics of the PSMA-targeted theranostic tandem. This result was confirmed by successful translation into first-in-humans application., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

68Ga-FAPI-PET/computed tomography (CT) is a novel PET/CT radiotracer particularly developed for oncologic imaging. Gynecologic malignancies comprise a broad spectrum of entities and, along with breast cancer, constitute cancers occurring exclusively or primarily, respectively, in women. Thus, a tracer designed not only for one but multiple malignancies has theoretic attractions. Even in comparison with 18F-FDG, the current standard oncologic tracer of nuclear medicine, 68Ga-FAPI, has demonstrated advantages in several tumors. As breast cancer, ovarian cancer, and cervical cancer are among the most common tumor types in women and are often accompanied by high morbidity as well as mortality rates, a reliable staging tool is paramount for optimal therapeutic management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Like other major cancers, gastric cancer expresses fibroblast activation protein (FAP) in cancer-associated fibroblasts. Many recent studies have reported the utility and superiority of FAP inhibitor (FAPI)-PET over [ 18 F]fluorodeoxyglucose (FDG)-PET in gastric cancers, from initial staging to recurrence detection. FAPI-PET shows higher accumulation in primary sites and metastatic lesions than does FDG-PET, especially for the detection of peritoneal carcinomatosis. In the case of gastric signet ring cell carcinoma, FAPI-PET showed excellent performance, as uptake is usually weak on FDG-PET in this cohort., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fibroblast activation protein (FAP)-targeted radioligand therapy offers a possibility of a novel cancer therapeutic strategy, aiming at tumor stroma1. Early clinical translations of FAP-tracers occurred as early as in the 1990s using antibodies, without substantial achievement further than the clinical phase II trial. The essential step toward the theranostic approach, with a conceptual combination of diagnostic and therapeutic emitters in a specific tracer, began with the implementation of small-molecule FAP-enzyme inhibitors (FAPI) in 2018. Currently, FAPI-04 and FAPI-46, containing DOTA-chelators with the possibility of radionuclide combination (Ga-68, Y-90, and Lu-177), are the compounds most widely used in the theranostic regimen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Imaging devices such as PET/CT are becoming increasingly important in view of the growing range of innovative nuclear medicine diagnostic procedures. Since the procurement and commissioning as well as the ongoing operation of imaging devices leads to comparatively high costs, it is of great interest for clinics and practices to know the number of scans from which the (planned) device operation leads to a profit. In the following, we will introduce the breakeven point analysis and present a calculation tool that users in nuclear medicine clinics and practices can use in everyday operations using PET/CT as an example., Methods: In the breakeven point analysis, the intersection point is determined from which the organisation- or device-specific revenues exceed the total costs incurred for personnel, material resources, etc. For this purpose, the fixed and variable (planned) cost components for the procurement and operation of the device must be prepared on the cost side and the respective device-related (planned) revenue structure on the revenue side., Results: The authors present the break-even analysis method with the data processing required for this using the example of the planned procurement or ongoing operation of a PET/CT. In addition, a calculation tool was developed, that interested users can use to prepare a device-specific break-even analysis. For this purpose, various cost and revenue data are discussed, which have to be compiled and processed within the clinic and entered into prepared spreadsheets., Conclusion: The breakeven point analysis can be used to determine the profit/loss (point) for the (planned) operation of imaging devices such as PET/CT. Users from imaging clinics/practices and administration can adapt the calculation tool presented to their specific facility and thus use it as a basic document for both the planned procurement and the ongoing operational control of imaging devices in everyday clinical practice., Competing Interests: Interessenkonflikt: Alle Autoren geben an, dass Sie bezüglich dieses Artikels keine Interessenkonflikte haben. Disclosures: Frederik L. Giesel ist Berater bei ABX, SOFIE Biosciences und Telix und hält geringe Patentanteile von F18-PSMA-1007 und FAP-liganden., (Thieme. All rights reserved.)

Aim/purpose: 18 F-labeled PSMA ligands offer various advantages as PET tracers over 68 Ga-labeled PSMA counterparts. Especially, an improved spatial resolution leads to improved detection rates of smaller prostate cancer (PCa) lesions. However, physiological PSMA uptake of ganglia of the sympathetic trunk can be quickly misinterpreted as possible PSMA-positive lymph node metastases. The aim of this retrospective study is to investigate [ 18 F]PSMA-1007 uptake and its intra-individual reproducibility in ganglia of the sympathetic trunk., Methods: We retrospectively included 28 consecutive patients (median age 69 ± 9 with a range of 49-90) with biochemical recurrence of PCa who underwent [ 18 F]PSMA-1007 PET/CT scan and, accordingly, a follow-up examination between August 2018 and August 2021. Cervical, coeliac, and sacral ganglia were identified on the iterative PET reconstructions and correlated with CT component. Tracer uptake of ganglia was determined by measuring SUV max and SUV mean values. Anatomical position of the ganglia in relation to adjacent vertebral bodies were noted. Statistical analyses were conducted using two-way repeated measures ANOVA and descriptive statistics., Results: The highest [ 18 F]PSMA-1007 uptake was found in coeliac ganglia followed by cervical and sacral ganglia. The SUV max in coeliac ganglia was 3.13 ± 0.85 (follow-up scan 3.11 ± 0.93), in cervical ganglia 2.73 ± 0.69 (follow-up scan 2.67 ± 0.74), and in sacral ganglia 1.67 ± 0.50 (follow-up scan 1.64 ± 0.52). The SUV mean in coeliac ganglia was 2.28 ± 0.64 (follow-up scan 2.28 ± 0.66), in cervical ganglia 1.62 ± 0.43 (follow-up scan 1.61 ± 0.43) and in sacral ganglia 1.15 ± 0.33 (follow-up scan 1.12 ± 0.34). In a given ganglion station, there was no statistically significant difference of SUV max or SUV mean values between baseline and follow-up scans., Conclusions: The first systematically described physiological [ 18 F]PSMA-1007 uptake in ganglia of the sympathetic trunk showed a low variability of SUV max or SUV mean and a good intra-individual reproducibility of [ 18 F]PSMA-1007 uptake in follow-up scans. These findings might improve and guide the differentiation of ganglia from possible malignant lesions., (© 2022. The Author(s).)