[Clinical significance of neuroendocrine tumors : Incidence, symptoms, diagnosis, stage, and prognostic factors and their influence on disease management]. / Klinische Bedeutung von neuroendokrinen Tumoren : Häufigkeit, Symptome, Diagnose und Stadien und prognostische Faktoren und deren Einfluss auf das Krankheitsmanagement.

BACKGROUND: Neuroendocrine neoplasms (NEN) are heterogenous with an increasing incidence in recent years. OBJECTIVES: Overview on incidence, symptoms, diagnostics, grading, imaging and prognostic determinants, including factors having an impact on therapeutic management. METHODS: Review on current literature, including original articles, reviews, guidelines and expert opinions. RESULTS: NEN are mainly located in the gastrointestinal tract and their incidence has increased in recent years, mainly due to improved diagnostics, e.g., cross-sectional imaging. Clinical characteristics include hormone excess syndromes (carcinoid syndrome). Laboratory markers such as chromogranin A are commonly used as part of routine diagnostics, followed by endoscopic and endosonographic procedures, which also allow biopsies to be obtained. Tumor spread can be determined by contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) or somatostatin receptor (SSRT)-PET/CT (positron emission tomography). Prognostic factors include Ki67 index, type, and grading. Resection with curative intent is the therapy of choice. In a metastasized setting, SSRT-directed treatment approaches are favored, while in dedifferentiated NEN, conventional chemotherapy is needed. CONCLUSION: A broad diagnostic armamentarium can be offered to NEN patients and the improved diagnostic procedures have most likely caused a raising incidence in recent years. Among others, prognostic factors are Ki67 and NEN subtypes; these clinical determinants also have an impact on patient management.

Prostate-specific Membrane Antigen: Diagnostics.

Since its clinical introduction in May 2011, prostate-specific membrane antigen (PSMA)-PET/computed tomography has quickly gained worldwide recognition as a significant breakthrough in prostate cancer diagnostics. In the meantime, several new PSMA radioligands for PET imaging have been introduced into routine clinical practice. This article aims to introduce the most commonly used tracers and their key areas of application.

The cutting edge: Promising oncology radiotracers in clinical development.

Molecular imaging moves forward with the development of new imaging agents, and among these are new radiotracers for nuclear medicine applications, particularly positron emission tomography (PET). A number of new targets are becoming accessible for use in oncologic applications. In this review, major new radiotracers in clinical development are discussed. Prominent among these is the family of fibroblast-activation protein-targeted agents that interact with the tumor microenvironment and may show superiority to 2-deoxy-2-[18F]fluoro-d-glucose in a subset of different tumor histologies. Additionally, carbonic anhydrase IX (CAIX) inhibitors are directed at clear cell renal cell carcinoma, which has long lacked an effective PET imaging agent. Those CAIX agents may also have utility in hypoxic tumors. Pentixafor, which binds to a transmembrane receptor, may similarly allow for visualization by PET of low-grade lymphomas, as well as being a second agent for multiple myeloma that opens theranostic possibilities. There are new adrenergic agents aimed at providing a PET-visible replacement to the single-photon-emitting radiotracer meta-[123I]iodobenzylguanidine (MIBG). Finally, in response to a major development in oncologic chemotherapy, there are new radiotracers targeted at assessing the suitability or use of immunotherapeutic agents. All of these and the existing evidence for their utility are discussed.

FAPI-PET in Cardiovascular Disease.

PET probes targeting fibroblasts are frequently used for varying applications in oncology. In recent years, the clinical spectrum has been expanded towards cardiovascular medicine, e.g., after myocardial infarction, in aortic stenosis or as a non-invasive read-out of atherosclerosis. We herein provide a brief overview of the current status of this PET radiotracer in the context of cardiovascular disease, including translational and clinical evidence. In addition, we will also briefly discuss future applications, e.g., the use of fibroblast-targeting PET to investigate bilateral organ function along the cardiorenal axis.

Prognostic Performance of RECIP 1.0 Based on [18F]PSMA-1007 PET in Prostate Cancer Patients Treated with [177Lu]Lu-PSMA I&T.

In metastatic castration-resistant prostate cancer (mCRPC) patients treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), the recently proposed criteria for evaluating response to PSMA PET (RECIP 1.0) based on 68Ga- and 18F-labeled PET agents provided prognostic information in addition to changes in prostate-specific antigen (PSA) levels. Our aim was to evaluate the prognostic performance of this framework for overall survival (OS) in patients undergoing RLT and imaged with [18F]PSMA-1007 PET/CT and compare the prognostic performance with the PSA-based response assessment. Methods: In total, 73 patients with mCRPC who were scanned with [18F]PSMA-1007 PET/CT before and after 2 cycles of RLT were retrospectively analyzed. We calculated the changes in serum PSA levels (ΔPSA) and quantitative PET parameters for the whole-body tumor burden (SUVmean, SUVmax, PSMA tumor volume, and total lesion PSMA). Men were also classified following the Prostate Cancer Working Group 3 (PCWG3) criteria for ΔPSA and RECIP 1.0 for PET imaging response. We performed univariable Cox regression analysis, followed by multivariable and Kaplan-Meier analyses. Results: Median OS was 15 mo with a median follow-up time of 14 mo. Univariable Cox regression analysis provided significant associations with OS for ΔPSA (per percentage, hazard ratio [HR], 1.004; 95% CI, 1.002-1.007; P < 0.001) and PSMA tumor volume (per unit, HR, 1.003; 95% CI, 1.000-1.005; P = 0.03). Multivariable Cox regression analysis confirmed ΔPSA (per percentage, HR, 1.004; 95% CI, 1.001-1.006; P = 0.006) as an independent prognosticator for OS. Kaplan-Meier analyses provided significant segregation between individuals with versus those without any PSA response (19 mo vs. 14 mo; HR, 2.00; 95% CI, 0.95-4.18; P = 0.04). Differentiation between patients with or without progressive disease (PD) was also feasible when applying PSA-based PCWG3 (19 mo vs. 9 mo for non-PD and PD, respectively; HR, 2.29; 95% CI, 1.03-5.09; P = 0.01) but slightly failed when applying RECIP 1.0 (P = 0.08). A combination of both response systems (PCWG3 and RECIP 1.0), however, yielded the best discrimination between individuals without versus those with PD (19 mo vs. 8 mo; HR, 2.78; 95% CI, 1.32-5.86; P = 0.002). Conclusion: In patients with mCRPC treated with RLT and imaged with [18F]PSMA-1007, frameworks integrating both the biochemical (PCWG3) and PET-based response (RECIP 1.0) may best assist in identifying subjects prone to disease progression.

MRVAS Score-introducing a standardized magnetic resonance scoring system for assessing the extent of inflammatory burden in giant cell arteritis.

OBJECTIVES: Our aim was to introduce a standardized system for assessing the extent of giant cell arteritis (GCA) on MRI, titled MRVAS (MR Vasculitis Activity score). To obtain a comprehensive view, we used an extensive MRI protocol including cranial vessels and the aorta with its branches. To test reliability, MRI was assessed by 4 readers with different levels of experience. METHODS: 80 patients with suspected GCA underwent MRI of cranial arteries and the aorta/branches (20 vessel segments). Every vessel was rated dichotomous [inflamed (coded as 1) or not 0], providing a summed score from 0 to 20. Blinded readers (two experienced radiologists [ExR], two inexperienced radiologists [InR]) applied the MRVAS on an individual vessel and an overall level (defined as the highest score of any of the individual vessel scores). To determine interrater agreement, Cohen's kappa was calculated for pairwise comparison of each reader for individual vessel segments. Intraclass correlation coefficients (ICC) were used for the MRVAS score. RESULTS: Concordance rates were excellent for both sub-cohorts on an individual vessel-based (GCA, ICC, 0.95; and non-GCA, ICC, 0.96) and Overall MRVAS score level (GCA, ICC, 0.96; and non-GCA, ICC, 1.0). Interrater agreement yielded significant concordance (p< 0.001) for all pairs (kappa range 0.78-0.98). No significant differences between ERs and IRs were observed (p= 0.38). CONCLUSION: The proposed MRVAS score allows standardized scoring of inflammation in GCA and achieved high agreement rates in a prospective setting.

Volumetric Parameters Derived from CXCR4-Directed PET/CT Predict Outcome in Patients with Gastrointestinal Neuroendocrine Carcinomas.

BACKGROUND: Gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs) are an aggressive subgroup of neuroendocrine neoplasms (NENs). In patients affected with NEN, there is a growing body of evidence that increased C-X-C motif chemokine receptor (CXCR4) expression is linked to decreasing overall survival (OS) in an ex-vivo setting. Thus, we aimed to determine whether the in-vivo-derived CXCR4-directed whole-body PET signal can also determine GEP-NEC patients with shorter OS. METHODS: We retrospectively included 16 patients with histologically proven GEP-NEC, who underwent CXCR4-directed PET/CT for staging and therapy planning. We assessed maximum, peak, and mean standardized uptake values as well as whole-body tumor volume (TV) and total-lesion uptake (TLU = SUVmean × TV) using a semi-automatic segmentation tool with a 50% threshold. Association of PET-based biomarkers and OS or radiographic progression-free survival (rPFS; according to RECIST 1.1 criteria) was analyzed using univariable and multivariable cox regression. RESULTS: Median OS and rPFS was 7.5 and 7 months, respectively. A significant correlation between TV and TLU was found for OS (TV: hazard ratio (HR) 1.007 95% confidence interval (CI) 1.000-1.014, p = 0.0309; TLU: HR 1.002 95% CI 1.000-1.003, p = 0.0350) and rPFS (TV: HR 1.010 95% CI 1.002-1.021; p = 0.0275; TLU: HR 1.002 95% CI 1.000-1.004, p = 0.0329), respectively. No significant correlation with OS or rPFS was found for non-volumetric parameters (p > 0.4). TV remained a significant predictive marker for OS and rPFS in multivariable analysis (OS: HR 1.012 95%, CI 1.003-1.022, p = 0.0084; rPFS: HR 1.009, 95% CI 0.9999-1.019, p = 0.0491), whereas TLU remained only prognostic for OS (HR 1.009, 95% CI 0.9999-1.019, p = 0.0194) but narrowly failed significance for rPFS (p = 0.0559). CONCLUSION: In-vivo assessment of CXCR4 PET-derived volumetric parameters is predictive for outcome of patients with GEP-NEC and could be used as a risk stratification tool, which detects patients prone to early progression.

Prognostic role of quantitative [18F]FDG PET/CT parameters in adrenocortical carcinoma.

PURPOSE: We aimed to evaluate the prognostic potential of baseline [18F]FDG PET/CT for overall survival (OS) in patients with adrenocortical carcinoma (ACC). METHODS: We performed a retrospective analysis of 67 treatment-naïve ACC patients with available [18F]FDG PET/CT at time of initial diagnosis. Pretherapeutic PETs of primary tumors were manually segmented and quantitative parameters (maximum/mean/peak standardized uptake value (SUVmax/mean/peak), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG, defined as TV*SUVmean) were derived. Based on a visual read, absence (M0) or presence of metastatic disease (M1) were evaluated. Kaplan-Meier and Cox regression analyses were used to determine the prognostic value of the above mentioned markers on overall survival adjusted for established prognostic markers. RESULTS: 24/67 patients (36%) presented with M0 based on PET/CT, while the remaining 43/67 (64%) had M1-status. 32/67 patients died during follow-up and median OS was 48 months. In 12% of patients FDG-PET detected additional metastatic lesion not clearly visible by CT only. In univariable analysis, all quantitatively derived PET parameters failed to reach significance (P ≥ 0.1), and only PET/CT-based M1-status and Ki-67 were associated with increased mortality (M1: HR 13.89, 95% CI 4.15-86.32, P < 0.001; Ki-67 HR 1.29, 95% CI 1.16-1.42; P < 0.0001). Using multivariable Cox regression analyses, M1-status (HR 9.69, 95% CI 2.82-60.99) and Ki-67 index (HR 1.29, 95% CI 1.13-1.04; P < 0.05) remained significant associated with OS. CONCLUSION: In treatment-naïve ACC patients, the quantitative PET parameter failed to predict OS, but presence of metastases detected by [18F]FDG PET/CT and Ki-67 index were independently associated with shorter OS. Therefore, a simple visual PET-based read-out is of prognostic value at initial diagnosis, while time-consuming PET-based quantification can be omitted.

Exploring Theranostic Avenues in Adrenocortical Carcinoma Using Chemokine Receptor and Prostate-Specific Membrane Antigen-Directed PET/CT.

ABSTRACT: We report on an adrenocortical carcinoma (ACC) patient, which has exhausted previous treatment options and was scheduled for prostate-specific membrane antigen (PSMA)- and C-X-C motif chemokine receptor 4 (CXCR4)-targeted PET/CT. We identified PSMA-avid pulmonary metastases exhibiting modest radiotracer accumulation, while chemokine receptor PET/CT provided intense uptake. This dual-tracer molecular imaging approach revealed that chemokine receptor PET appears to be more suitable in patients with advanced ACC, indicating that CXCR4-directed radioligand therapy may be considered in such patients suffering from end-stage disease. Given its dismal prognosis, chemokine receptor-directed theranostics may therefore extend the therapeutic armamentarium as last-line option in advanced ACC.

Monitoring Dual-Cancer Treatment in a Patient With Prostate and Hepatocellular Carcinoma Using Prostate-Specific Membrane Antigen-Directed PET/CT.

ABSTRACT: We report on a 70-year-old man affected with prostate carcinoma (PC) scheduled for prostate-specific membrane antigen (PSMA) PET/CT using 18 F-PSMA1007. Because of uptake in the liver and corresponding findings on magnetic resonance, diagnosis of hepatocellular carcinoma (HCC, G1) was established. The patient was then scheduled for antihormonal treatment for PC and locoregional therapy due to HCC. On follow-up PSMA-targeted PET/CT, we observed durable response to PC-associated therapy, whereas hepatic lesions showed progressive disease. As such, we herein report on a dual-cancer targeting molecular imaging strategy to determine disease extent in a patient affected with both PC and HCC, along with potential of monitoring both systemic and locoregional treatment.

Positron Emission Tomography/Computed Tomography Transformation of Oncology: Multiple Myeloma.

This article provides a comprehensive review of the role of 2-deoxy-2-[18F]fluoro-d-glucose (18F FDG) positron emission tomography/computed tomography (PET/CT) in multiple myeloma (MM) and related plasma cell disorders. MM is a hematologic malignancy characterized by the neoplastic proliferation of plasma cells. 18F FDG PET/CT integrates metabolic and anatomic information, allowing for accurate localization of metabolically active disease. The article discusses the use of 18F FDG PET/CT in initial diagnosis, staging, prognostication, and assessing treatment response. Additionally, it provides valuable insights into the novel imaging targets including chemokine receptor C-X-C motif 4 and CD38.

Evaluating the Patterns of FAPI Uptake in the Shoulder Joint: a Preliminary Study Comparing with FDG Uptake in Oncological Studies.

BACKGROUND: Fibroblast activation protein inhibitor (FAPI) targeting PET has been introduced as a novel molecular imaging modality for visualizing cancer-associated fibroblasts. There have also been reports suggesting incidental findings of localized accumulation in the shoulder joints. However, further characterization in a larger patient cohort is still lacking. METHODS: 77 consecutive patients (28 females; mean age, 63.1 ± 11.6) who underwent Ga-68 FAPI-04 PET/CT for diagnosis of solid tumors were included. The incidence and localization of tracer uptake in shoulder joints were investigated and compared with available F-18 FDG scans serving as reference. RESULTS: Ga-68 FAPI-04 uptake was evaluated in 77 patients (154 shoulder joints), of whom 54 subjects (108 shoulder joints) also had available F-18 FDG scans for head-to-head comparison. On FAPI-targeted imaging, 67/154 shoulders (43.5%) demonstrated increased radiotracer accumulation in target lesions, which were distributed as follows: acromioclavicular (AC) joints in 25/67 (37.3%), followed by glenohumeral and subacromial (GH + SA) joints in 23/67 (34.3%), or both (AC and GH + SA joints) in the remaining 19/67 (28.4%). Ga-68 FAPI-04 correlated with quantified F-18 FDG uptake (r = 0.69, p < 0.0001). Relative to the latter radiotracer, however, in-vivo FAP expression in the shoulders was significantly increased (Ga-68 FAPI-04, 4.7 ± 3.2 vs F-18 FDG, 3.6 ± 1.3, p < 0.001). CONCLUSION: Our study revealed focal accumulation of Ga-68 FAPI-04 in the shoulders, particularly in the AC joints, with higher uptake compared to the inflammatory-directed PET radiotracer F-18 FDG in oncological studies. As a result, further trials are warranted to investigate the potential of FAPI-directed molecular imaging in identifying chronic remodeling in shoulder joints. This could have implications for initiating anti-FAP targeted photodynamic therapy based on PET signal strength.

C-X-C Motif Chemokine Receptor 4-Targeted Radioligand Therapy in Hematological Malignancies-Myeloablative Effects, Antilymphoma Activity, and Safety Profile.

BACKGROUND: After C-X-C motif chemokine receptor 4 (CXCR4)-directed radioligand therapy (RLT), lymphoma patients are scheduled for conditioning therapy (CON) followed by hematopoietic stem cell transplantation (HSCT). We aimed to determine whether CXCR4-RLT can achieve bone marrow ablation and direct antilymphoma activity independent from CON/HSCT and also evaluated the safety profile of this theranostic approach in an acute setting. PATIENTS AND METHODS: After CXCR4-directed 68 Ga-pentixafor PET/CT, 21 heavily pretreated patients with hematological malignancies underwent CXCR4-directed RLT using 90 Y-pentixather. The extent of myeloablative efficacy was determined by investigating hematologic laboratory parameters before RLT (day -1), at the day of RLT (day 0), 2 days after RLT (day 2), and before CON (median day 10). Serving as surrogate marker of antilymphoma activity, lactate dehydrogenase (LDH) levels were also assessed until CON. We also screened for laboratory-defined tumor lysis syndrome after the Cairo-Bishop definition and recorded acute laboratory adverse events using the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: After RLT, we observed a significant decline of leukocyte levels by 79.4% ± 18.7% till CON (granulocytes, drop by 70.3% ± 21%; platelets, reduction by 43.1% ± 36%; P ≤ 0.0005 vs day 0, respectively). After RLT, LDH levels already reached a peak at day 2, which was followed by a rapid decline thereafter (peak vs day of CON, P = 0.0006), indicating that 90 Y-pentixather exhibits direct antilymphoma activity. At day of CON, LDH levels were also significantly lower when compared with day -1 ( P = 0.04), suggestive for durable response mediated by RLT. No patient fulfilled the criteria of tumor lysis syndrome, whereas 25 laboratory adverse events attributable to CXCR4-directed treatment were identified (≥grade 3 in 2/25 [8%]). During further treatment course, all patients (100%) received HSCT. CONCLUSIONS: CXCR4-directed RLT causes effective myeloablation, which allows for HSCT. In addition, it also exerts direct antilymphoma activity independent of subsequent therapeutic steps, whereas safety profile was acceptable.

CXCR4-directed PET/CT with [68 Ga]Ga-pentixafor in solid tumors-a comprehensive analysis of imaging findings and comparison with histopathology.

BACKGROUND: C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings. METHODS: A total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [68 Ga]Ga-pentixafor (total number of scans, 152). A semi-quantitative analysis of the CXCR4-positive tumor burden including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) using blood pool was conducted. In addition, we performed histopathological staining to determine the immuno-reactive score (IRS) from patients' tumor tissue and investigated possible correlations with SUVmax (by providing Spearman's rho ρ). Based on imaging, we also assessed the eligibility for CXCR4-targeted radioligand therapy or non-radioactive CXCR4 inhibitory treatment (defined as more than five CXCR4-avid target lesions [TL] with SUVmax above 10). RESULTS: One hundred three of 152 (67.8%) scans showed discernible uptake above blood pool (TBR > 1) in 462 lesions (52 primary tumors and 410 metastases). Median TBR was 4.4 (1.05-24.98), thereby indicating high image contrast. The highest SUVmax was observed in ovarian cancer, followed by small cell lung cancer, desmoplastic small round cell tumor, and adrenocortical carcinoma. When comparing radiotracer accumulation between primary tumors and metastases for the entire cohort, comparable SUVmax was recorded (P > 0.999), except for pulmonal findings (P = 0.013), indicative for uniform CXCR4 expression among TL. For higher IRS, a weak, but statistically significant correlation with increased SUVmax was observed (ρ = 0.328; P = 0.018). In 42/103 (40.8%) scans, more than five TL were recorded, with 12/42 (28.6%) exhibiting SUVmax above 10, suggesting eligibility for CXCR4-targeted treatment in this subcohort. CONCLUSIONS: In a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [68 Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [68 Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy.

Chemokine receptor-targeted PET/CT provides superior diagnostic performance in newly diagnosed marginal zone lymphoma patients: a head-to-head comparison with [18F]FDG.

BACKGROUND: In patients with marginal zone lymphoma (MZL), [18F]FDG PET/CT provided inconsistent diagnostic accuracy. C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in MZL and thus, may emerge as novel theranostic target. We aimed to evaluate the diagnostic performance of CXCR4-targeting [68Ga]Ga-PentixaFor when compared to [18F]FDG PET/CT in MZL. METHODS: Thirty-two untreated MZL patients (nodal, n = 17; extranodal, n = 13; splenic, n = 2) received [68Ga]Ga-PentixaFor and [18F]FDG PET/CT within median 2 days. We performed a visual and quantitative analysis of the total lymphoma volume by measuring maximum/peak standardized uptake values (SUVmax/peak), and calculating target-to-background ratios (TBR, defined as lesion-based SUVpeak divided by SUVmean from blood pool). Visual comparisons for both radiotracers were carried out for all target lesions (TL), and quantitative analysis of concordant TL evident on both scans. Last, MZL subtype analyses were also conducted. RESULTS: On a patient-based level, [68Ga]Ga-PentixaFor identified MZL manifestations in 32 (100%) subjects (vs. [18F]FDG, 25/32 [78.1%]). Of the 256 identified TL, 127/256 (49.6%) manifestations were evident only on CXCR4-directed imaging, while only 7/256 (2.7%) were identified on [18F]FDG but missed by [68Ga]Ga-PentixaFor. In the remaining 122/256 (47.7%) concordant TL, [68Ga]Ga-PentixaFor consistently provided increased metrics when compared to [18F]FDG: SUVmax, 10.3 (range, 2.53-37.2) vs. 5.72 (2.32-37.0); SUVpeak, 6.23 (1.58-25.7) vs. 3.87 (1.54-27.7); P < 0.01, respectively. Concordant TL TBR on [68Ga]Ga-PentixaFor (median, 3.85; range, 1.05-16.0) was also approximately 1.8-fold higher relative to [18F]FDG (median, 2.08; range, 0.81-28.8; P < 0.01). Those findings on image contrast, however, were driven by nodal MZL (P < 0.01), and just missed significance for extranodal MZL (P = 0.06). CONCLUSIONS: In newly diagnosed MZL patients, [68Ga]Ga-PentixaFor identified more sites of disease when compared to [18F]FDG, irrespective of MZL subtype. Quantitative PET parameters including TBR were also higher on [68Ga]Ga-PentixaFor PET/CT, suggesting improved diagnostic read-out using chemokine receptor-targeted imaging.

Comparison of PET/CT-based eligibility according to VISION and TheraP trial criteria in end-stage prostate cancer patients undergoing radioligand therapy.

BACKGROUND: Two randomized clinical trials demonstrated the efficacy of prostate-specific membrane antigen (PSMA) radioligand therapy (PSMA RLT) in metastatic castration-resistant prostate cancer (mCRPC). While the VISION trial used criteria within PSMA PET/CT for inclusion, the TheraP trial used dual tracer imaging including FDG PET/CT. Therefore, we investigated whether the application of the VISION criteria leads to a benefit in overall survival (OS) or progression-free survival (PFS) for men with mCRPC after PSMA RLT. METHODS: Thirty-five men with mCRPC who had received PSMA RLT as a last-line option and who had undergone pretherapeutic imaging with FDG and [68Ga]Ga-PSMA I&T or [18F]PSMA-1007 were studied. Therapeutic eligibility was retrospectively evaluated using the VISION and TheraP study criteria. RESULTS: 26 of 35 (74%) treated patients fulfilled the VISION criteria (= VISION+) and only 17 of 35 (49%) fulfilled the TheraP criteria (= TheraP+). Significantly reduced OS and PFS after PSMA RLT was observed in patients rated VISION- compared to VISION+ (OS: VISION-: 3 vs. VISION+: 12 months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.1, p < 0.01; PFS: VISION-: 1 vs. VISION+: 5 months, HR 2.7, 95% CI 1.0-7.8, p < 0.01). For patients rated TheraP-, no significant difference in OS but in PFS was observed compared to TheraP+ patients (OS: TheraP-: 5.5 vs. TheraP+: 11 months, HR 1.6, 95% CI 0.8-3.3, p = 0.2; PFS: TheraP-: 1 vs. TheraP+: 6 months, HR 2.2, 95% CI 1.0-4.5, p < 0.01). CONCLUSION: Retrospective application of the inclusion criteria of the VISION study leads to a benefit in OS and PFS after PSMA RL, whereas TheraP criteria appear to be too strict in patients with end-stage prostate cancer. Thus, performing PSMA PET/CT including a contrast-enhanced CT as proposed in the VISION trial might be sufficient for treatment eligibility of end-stage prostate cancer patients.

[18F]FDG PET/CT can trigger relevant oncological management changes leading to favorable outcome in iodine-negative thyroid cancer patients.

BACKGROUND: In patients with iodine-negative thyroid cancer (TC), current guidelines endorse an [18F]FDG PET/CT to identify dedifferentiated sites of disease. We aimed to determine the rate of oncological management changes triggered by such a molecular imaging approach, along with the impact on outcome. METHODS: 42 consecutive patients with negative findings on [131I] whole body scan were scheduled for [18F]FDG PET/CT and treatment based on PET results were initiated. To determine the impact on oncological management, we compared the therapeutic plan prior to and after molecular imaging. Based on imaging follow-up, the rate of controlled disease (CD, defined as stable disease, complete or partial response) was also recorded, thereby allowing to assess whether [18F]FDG-triggered management changes can also lead to favorable outcome. RESULTS: We observed no alterations of the treatment plan in 9/42 (21.4%) subjects (active surveillance in 9/9 [100%]). Oncological management was changed in the remaining 33/42 (78.6%; systemic treatment in 9/33 [27.3%] and non-systemic treatment in 24/33 [72.7%]). Among patients receiving non-systemic therapy, the following changes were noted: surgery in 20/24 (83.3%) and radiation therapy in 4/24 (16.7%). In the systemic group, tyrosine kinase inhibitor (TKI) was prescribed in 8/9 (88.9%), while radioiodine therapy based on a TKI-mediated redifferentiation approach was conducted in 1/9 (11.1%). In 26 subjects with available follow-up, rate of CD was 22/26 (84.6%) and among those, 15/22 (68.1%) had experienced previous management changes based on PET/CT findings. CONCLUSIONS: In subjects with iodine-negative TC, [18F]FDG PET/CT triggered relevant management changes along with disease control in the vast majority of patients. As such, in dedifferentiated TC, [18F]FDG PET/CT may serve as a relevant management tool and therapeutic decision-aid in the clinic.

PSMA PET/CT for Response Assessment of 177Lu-PSMA Therapy.

Prostate-specific membrane antigen (PSMA) PET/CT has been widely integrated into the management of prostate cancer (PCa) patients with biochemical recurrence, is increasingly used for initial staging in high-risk patients prior to surgery or to identify candidates for PSMA-targeted radioligand therapy (RLT). To date, monitoring response in PCa patients in prospective studies remains the domain of conventional imaging, such as magnetic resonance/CT or bone scintigraphy. With the increasing use of PSMA-targeted PET/CT in PCa, however, varying criteria based on molecular imaging have been established to define progressive disease, including "PSMA PET Progression Criteria," "Response evaluation criteria in PSMA PET/CT (RECIP 1.0)" or consensus statements of respective societies. In the present review, we will discuss the current status of PSMA PET/CT for response monitoring, focusing on PSMA RLT with [177Lu]Lu-labeled PSMA ligands, along with a head-to-head comparison of recently published response criteria.

A Practical Guide to the Pearls and Pitfalls of PSMA PET Imaging.

Prostate-specific membrane antigen (PSMA)-targeted PET agents have revolutionized the care of patients with prostate cancer, supplanting traditional methods of imaging prostate cancer, and improving the selection and delivery of therapies. This has led to a rapid expansion in both the number of PSMA PET scans performed and the imaging specialists required to interpret those scans. To aid those imagers and clinicians who are new to the interpretation of PSMA PET, this review provides an overview of the interpretation of PSMA PET/CT imaging and pearls for overcoming commonly encountered pitfalls. We discuss the physiologic distribution of the clinically available PSMA-targeted radiotracers, the commonly encountered patterns of prostate cancer spread, as well as the benign and malignant mimics of prostate cancer. Additionally, we review the standardized PSMA PET reporting systems and the role of PSMA in selecting appropriate patients for PSMA-targeted therapies.