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Prospective results have demonstrated favorable safety and efficacy of [ 177 Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [ 177 Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ 2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [ 177 Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [ 177 Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [ 177 Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [ 177 Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [ 177 Lu]Lu-PSMA after a treatment break., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

[ 18 F]tetrafluoroborate ([ 18 F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [ 18 F]TFB PET with high-activity posttherapeutic [ 131 I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [ 18 F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [ 131 I]iodine therapy (range, 5.00-10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [ 18 F]TFB PET/CT 40 min after injection of a median of 321 MBq of [ 18 F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [ 131 I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [ 18 F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [ 131 I]iodine positive, 32 lesions were [ 18 F]TFB positive, and 52 were [ 18 F]FDG positive. Three of the 30 [ 131 I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [ 18 F]TFB uptake and [ 18 F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, -0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [ 18 F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [ 131 I]iodine scans. Therefore, it may help in the selection of patients for [ 131 I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [ 18 F]TFB uptake seems to be inversely correlated with [ 18 F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

In the VISION trial, [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) plus protocol-permitted standard of care significantly improved overall survival and radiographic progression-free survival compared with standard of care alone in patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer. This VISION dosimetry substudy quantified absorbed doses of 177 Lu-PSMA-617 in the kidneys and other organs. Methods: Participants were a separate cohort of 30 nonrandomized patients receiving standard of care plus 177 Lu-PSMA-617 at 7.4 GBq per cycle for up to 6 cycles. Blood samples, whole-body conjugate planar image scintigraphy, and abdominal SPECT/CT images were collected. SPECT/CT images were collected at 2, 24, 48, and 168 h after administration in cycle 1 and at a single time point 48 h after administration in cycles 2-6. Outcomes were absorbed dose per unit activity per cycle and cumulative absorbed dose over all cycles. Cumulative absorbed doses were predicted by extrapolation from cycle 1, and calculation of observed values was based on measurements of cycle 1 and cycles 2-6. Safety was also assessed. Results: Mean (±SD) absorbed doses per cycle in the kidneys were 0.43 ± 0.16 Gy/GBq in cycle 1 and 0.44 ± 0.21 Gy/GBq in cycles 2-6. The observed and predicted 6-cycle cumulative absorbed doses in the kidneys were 15 ± 6 and 19 ± 7 Gy, respectively. Observed and predicted cumulative absorbed doses were similar in other at-risk organs. Safety findings were consistent with those in the VISION study; no patients experienced renal treatment-emergent adverse events of a grade higher than 3. Conclusion: The renal cumulative absorbed 177 Lu-PSMA-617 dose was below the established limit. 177 Lu-PSMA-617 had a good overall safety profile, and low renal radiotoxicity was not a safety concern. Cumulative absorbed doses in at-risk organs over multiple cycles can be predicted by extrapolation from cycle 1 data in patients with metastatic castration-resistant prostate cancer receiving 177 Lu-PSMA-617., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

223 Ra-dichloride ( 223 Ra) and 177 Lu-prostate-specific membrane antigen (PSMA) are approved treatments for metastatic castration-resistant prostate cancer (mCRPC). The safety and effectiveness of sequential use of 223 Ra and 177 Lu-PSMA in patients with mCRPC are not well described. This study aimed to evaluate 177 Lu-PSMA safety and efficacy in patients with mCRPC previously treated with 223 Ra. Methods: The radium→lutetium (RALU) study was a multicenter, retrospective, medical chart review. Participants had received at least 1 223 Ra dose and, in any subsequent therapy line, at least 1 177 Lu-PSMA dose. Primary endpoints included the incidence of adverse events (AEs), serious AEs, grade 3-4 hematologic AEs, and abnormal laboratory values. Secondary endpoints included overall survival, time to next treatment/death, and change from baseline in serum prostate-specific antigen and alkaline phosphatase levels. Results: Data were from 133 patients. Before 177 Lu-PSMA therapy, 56% (75/133) of patients received at least 4 life-prolonging therapies; all patients received 223 Ra (73% received 5-6 injections). Overall, 27% (36/133) of patients received at least 5 177 Lu-PSMA infusions. Any-grade treatment-emergent AEs were reported in 79% (105/133) of patients and serious AEs in 30% (40/133). The most frequent grade 3-4 laboratory abnormalities were anemia (30%, 40/133) and thrombocytopenia (13%, 17/133). Median overall survival was 13.2 mo (95% CI, 10.5-15.6 mo) from the start of 177 Lu-PSMA. Conclusion: In this real-world setting, 223 Ra followed by 177 Lu-PSMA therapy in heavily pretreated patients with mCRPC was clinically feasible, with no indication of impairment of 177 Lu-PSMA safety or effectiveness., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

The radium lutetium (RALU) study evaluated the feasibility of sequential α- and β-emitter use in patients with bone-predominant metastatic castration-resistant prostate cancer. Methods: This preplanned interim retrospective analysis investigated safety and survival outcomes with 177 Lu-PSMA in patients treated with prior 223 Ra. Results: Forty-nine patients were evaluated. Patients received a median of 6 223 Ra injections; 59% of patients received at least 4 177 Lu-PSMA cycles. Most (69%) patients received at least 4 life-prolonging therapies before 177 Lu-PSMA. Common Terminology Criteria for Adverse Events grade 3-4 treatment-emergent adverse events during 177 Lu-PSMA therapy and a 30-d follow-up period included anemia (18%) and thrombocytopenia (2%). Median overall survival was 12.6 mo (95% CI, 8.8-16.1 mo) and 31.4 mo (95% CI, 25.7-37.6 mo) from starting 177 Lu-PSMA or 223 Ra, respectively. Conclusion: 177 Lu-PSMA treatment was well tolerated in patients who had received prior 223 Ra. 223 Ra use before 177 Lu-PSMA is feasible and can be considered for future assessment of the optimal treatment sequence., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Conventional imaging low-(LVD) versus high-volume disease (HVD) are associated with survival in metastatic hormone-sensitive prostate cancer (mHSPC) according to CHAARTED and STAMPEDE trials. We propose a compatible quantitative PSMA-PET framework for disease volume assessment in mHSPC. Methods: Three PET centers screened their PSMA-PET database for mHSPC patients. CT versus PSMA-PET stage, lesion number, and classification of LVD vs. HVD were determined by one blinded reader; PSMA-positive tumor volume (PSMA-TV) was quantified semi-automatically. Results: 85 CT-based CHAARTED-LVD and 20 CT-based CHAARTED-HVD patients were included. A PSMA-TV of ~40 ml was the optimal cutoff between CT-based CHAARTED-LVD (non-unifocal) and HVD (non-M1c) (AUC 0.86). Stratification into PET-LVD (unifocal or oligometastatic/disseminated <~40 mL) and PET-HVD (oligometastatic/disseminated ≥~40 mL or M1c) had 13% misalignment with CHAARTED criteria. Conclusion: PSMA-PET criteria with volume quantification deliver comparable LVD/HVD discrimination with additional subgroups for unifocal, oligometastatic and disseminated disease, critical for guidance of targeted or multimodal therapy., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Prostate-specific membrane antigen (PSMA)-ligand PET/CT is performed on patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. On the basis of clinical results, 18 F-PSMA-1007 is a promising PSMA PET tracer, but detailed histologic confirmation has been lacking. Methods: Ninety-six patients with prostate cancer underwent 18 F-PSMA-1007 PET/CT followed by either radical prostatectomy with lymphadenectomy or salvage lymphadenectomy. The histologic findings of PSMA PET-positive nodes were analyzed retrospectively. A lesion-based and patient-based analysis was performed comparing all positive lesions and only lesions larger than 3 mm on histopathology. Results: Of the patients, 90.6% received 18 F-PSMA-1007 PET/CT for staging before the primary treatment, whereas 9.4% underwent imaging for biochemical recurrence. In 34.4% of the cohort, positive lymph nodes were present on imaging. In total, 1,746 lymph nodes were dissected in 96 patients. 18 F-PSMA-1007 PET had a lesion-based sensitivity of 81.7%, a specificity of 99.6%, a positive predictive value of 92.4%, and a negative predictive value of 98.9% for detecting positive lymph nodes larger than 3 mm. In the analysis of all malignant nodes regardless of size, the overall sensitivity, specificity, positive predictive value, and negative predictive value on lesion-based analysis were 71.2%, 99.5%, 91.3%, and 97.9%, respectively. The patient-based analysis showed a sensitivity of 85.9% and a specificity of 99.5% for lymph nodes larger than 3 mm. Conclusion: 18 F-PSMA-1007 PET/CT reliably detects malignant lymph nodes and has an exceptional specificity of more than 99% for nodal metastases., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Prostate-specific membrane antigen (PSMA)-targeting PET imaging is becoming the reference standard for prostate cancer staging, especially in advanced disease. Yet, the implications of PSMA PET-derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be because semiautomated quantification of whole-body tumor volume as a PSMA PET biomarker is an unmet clinical challenge. Therefore, in the present study we propose and evaluate a software that enables the semiautomated quantification of PSMA PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype. PSMA-accumulating foci were automatically segmented by a percental threshold (50% of local SUV max ). Neural networks were trained to segment organs in PET/CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semiautomatically excluded from the analysis. Pretherapeutic PSMA PET/CTs of 40 consecutive patients treated with 177 Lu-PSMA-617 were evaluated in this analysis. The whole-body tumor volume (PSMA TV50 ), SUV max , SUV mean , and other whole-body imaging biomarkers were calculated for each patient. Semiautomatically derived results were compared with manual readings in a subcohort (by 1 nuclear medicine physician). Additionally, an interobserver evaluation of the semiautomated approach was performed in a subcohort (by 2 nuclear medicine physicians). Results: Manually and semiautomatically derived PSMA metrics were highly correlated (PSMA TV50 : R 2 = 1.000, P < 0.001; SUV max : R 2 = 0.988, P < 0.001). The interobserver agreement of the semiautomated workflow was also high (PSMA TV50 : R 2 = 1.000, P < 0.001, interclass correlation coefficient = 1.000; SUV max : R 2 = 0.988, P < 0.001, interclass correlation coefficient = 0.997). PSMA TV50 (ml) was a significant predictor of overall survival (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006 P = 0.004). Conclusion: PSMA TV50 is a promising PSMA PET biomarker that is reproducible and easily quantified by the proposed semiautomated software. Moreover, PSMA TV50 is a significant predictor of overall survival in patients with advanced prostate cancer who receive 177 Lu-PSMA-617 therapy., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

The aim of this study was to evaluate the efficacy of 177 Lu-prostate-specific membrane antigen (PSMA)-617 ( 177 Lu-PSMA) and selective internal radiation therapy (SIRT) for the treatment of liver metastases of castration-resistant prostate cancer. Methods: Safety and survival of patients with metastatic castration-resistant prostate cancer and liver metastases assigned to 177 Lu-PSMA alone ( n = 31) or in combination with SIRT ( n = 5) were retrospectively analyzed. Additionally, a subgroup ( n = 10) was analyzed using morphologic and molecular response criteria. Results: Median estimated survival was 5.7 mo for 177 Lu-PSMA alone and 8.4 mo for combined sequential 177 Lu-PSMA and SIRT. 177 Lu-PSMA achieved discordant therapy responses with both regressive and progressive liver metastases in the same patient (best vs. worst responding metastases per patient: -35% vs. +63% diameter change; P < 0.05). SIRT was superior to 177 Lu-PSMA for the treatment of liver metastases (0% vs. 56% progression). Conclusion: The combination of 177 Lu-PSMA and SIRT is efficient and feasible for the treatment of advanced prostate cancer. 177 Lu-PSMA alone seems to have limited response rates in the treatment of liver metastases., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Prostate-specific membrane antigen (PSMA) is of considerable interest as a target for diagnostics and therapy of prostate cancer patients. PSMA-targeted imaging has demonstrable value in guiding the management of the clinical evolution of prostatic cancer. The use of PSMA-targeted therapy using 177 Lu-labeled PSMA-617 is similarly effective and is progressing toward approval. The phase III VISION trial represents the largest well-designed and executed study of a theranostic pair. This article provides an overview of the phase III trial and delineates the different study arms and their implications in the assessment of efficacy. The VISION (phase III) trial will provide data of critical value to the field of theranostics and especially the field of prostatic cancer management., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

177 Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using inhibitors of PSMA is a novel therapeutic option in patients with metastatic castration-resistant prostate cancer. The current literature suggests that this therapy is well tolerated and effective. On the basis of clinical need and current evidence, the therapy is being implemented in a growing number of centers worldwide. Here, we review important aspects of 177 Lu-PSMA RLT, including patient stratification, the therapy protocol, concomitant medication, and follow-up, to inform medical staff involved in the RLT and care of patients with metastatic castration-resistant prostate cancer., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

177 Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177 Lu-PSMA-617 in a large cohort of patients., Methods: One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with 177 Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline ≥ 50% from baseline to at least 2 wk after the start of RLT., Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response., Conclusion: The present retrospective multicenter study of 177 Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: Radiolabeled prostate-specific membrane antigen (PSMA) ligands represent a true theranostic concept for diagnosis and therapy in patients with relapsed or metastatic prostate cancer. The aim of this study was to evaluate the response to and tolerability of a single dose of (177)Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC)., Methods: The data of 82 consecutive patients (median age, 73 y; range, 43-87 y) with mCRPC who received a single dose of (177)Lu-PSMA-617 (mean, 5.9 ± 0.5 GBq) were retrospectively analyzed. Data were collected at baseline and 8 wk after therapy. (68)Ga-PSMA-11 PET/CT was performed on all patients to verify sufficient PSMA expression. Bone, lymph node, liver, and lung metastases were present in 99%, 65%, 17%, and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data, and the prostate-specific antigen (PSA) level at baseline and 8 wk after therapy application., Results: Six patients died, and 2 patients dropped out because they were not willing to continue therapy and follow-up. The complete dataset of 74 patients was available for analysis. Forty-seven patients (64%) showed a PSA decline, including 23 (31%) with a decline by more than 50%. Thirty-five patients (47%) had stable disease: the change in their PSA level ranged from less than a 50% decline to less than a 25% rise. Seventeen patients (23%) had progressive disease: their PSA level rose by more than 25%. There were no significant changes in hemoglobin, white blood cells, creatinine, or tubular extraction rates indicative of toxicity. There was a significant but mild decrease in platelets, but the median value was still within the reference range., Conclusion: This retrospective multicenter analysis suggests that radioligand therapy with (177)Lu-PSMA-617 is safe and well tolerated and has a considerable effect on PSA level. Therefore, it offers an additional therapeutic option for patients with mCRPC. These data may justify further prospective randomized studies to evaluate and prove the clinical benefit in terms of survival and quality of life., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: We evaluated the diagnostic value and accuracy of prostate-specific membrane antigen (PSMA) PET for the intraprostatic delineation of prostate cancer before prostatectomy., Methods: We identified 6 patients with biopsy-proven high-risk prostate cancer who were referred for (68)Ga-PSMA PET/CT before radical prostatectomy to rule out metastasis. After prostatectomy, a histologic map of the prostate was reconstructed. The histologic extent and Gleason score of each segment of the prostate were compared with (68)Ga-PSMA PET images resliced to the histologic axis. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated. The SUV of each segment was measured, and median values were compared., Results: Of the 132 segments, 112 were eligible for analysis. The correlation of histologic results with (68)Ga-PSMA PET images showed a specificity and sensitivity of 92%. The positive and negative likelihood ratio and the positive and negative predictive value for detection of prostate cancer on (68)Ga-PSMA PET were 11.5, 0.09, 96%, and 85%, respectively. The median SUVmax of true-positive prostate segments was significantly higher than that of true-negative segments (11.0 ± 7.8 vs. 2.7 ± 0.9, P< 0.001), and a cutoff of 4 revealed a sensitivity and specificity of 86.5% and an accuracy of 87.5%., Conclusion: These preliminary results show that the intraprostatic localization and extent of prostate cancer may be estimated by (68)Ga-PSMA PET. This imaging method may be helpful for identifying target lesions before prostate biopsy and may support decision making before focal or radical therapy., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: In the diagnostic algorithm of cardiac tumors, the noninvasive determination of malignancy and metastatic spread is of major interest to stratify patients and to select and monitor therapies. In the diagnostic work-up, morphologic imaging modalities such as echocardiography or magnetic resonance tomography offer information on, for example, size, invasiveness, and vascularization. However, preoperative assessment of malignancy may be unsatisfactory. The aim of this study was to evaluate the diagnostic value of (18)F-FDG PET and the incremental diagnostic value of an optimized CT score in this clinical scenario., Methods: (18)F-FDG PET/CT scans (whole-body imaging with low-dose CT) of 24 consecutive patients with newly diagnosed cardiac tumors were analyzed (11 men, 13 women; mean age ± SD, 59 ± 13 y). The maximum standardized uptake values (SUV(max)) of the tumors were measured. Patients were divided into 2 groups: benign cardiac tumors (n = 7) and malignant cardiac tumors (n = 17) (cardiac primaries [n = 8] and metastases [n = 9]). SUV(max) was compared between the 2 groups. Results were compared with contrast-enhanced CT, using standardized criteria of malignancy. Histology served as ground truth., Results: Mean SUV(max) was 2.8 ± 0.6 in benign cardiac tumors and significantly higher both in malignant primary and in secondary cardiac tumors (8.0 ± 2.1 and 10.8 ± 4.9, P < 0.01). Malignancy was determined with a sensitivity of 100% and specificity of 86% (accuracy, 96%), after a cutoff with high sensitivity (SUV(max) of 3.5) was chosen to avoid false-negatives. Morphologic imaging reached a sensitivity of 82% and a specificity of 86% (accuracy, 83%). Both false-positive and false-negative decisions in morphology could be corrected in all but 1 case using a metabolic threshold with an SUV(max) of 3.5. In addition, extracardiac tumor manifestations were detected in 4 patients by whole-body (18)F-FDG PET/CT., Conclusion: (18)F-FDG PET/CT can aid the noninvasive preoperative determination of malignancy and may be helpful in detecting metastases of malignant cardiac tumors.

Unlabelled: The purpose of this retrospective study was to evaluate the role of (18)F-FDG PET or PET/CT in the prediction of patient outcome in children and young adults affected by rhabdomyosarcoma., Methods: Forty-one patients with histology-proven rhabdomyosarcoma who underwent PET or PET/CT were identified (age range, 1-20 y; mean age ± SD, 9.9 ± 5.8 y). Tumor maximum standardized uptake value (SUV(max)) and visually rated metabolic activity, as well as the presence of metabolically active lymph nodes and distant metastases, were compared with event-free and overall survival. Multivariate Cox regression analyses were performed to compare the prediction of outcome according to metabolic tumor intensity in relation to established prognostic factors., Results: Kaplan-Meier analyses revealed a significantly shorter overall survival in primary tumors visually rated as highly metabolically active or with a ratio of SUV(max) to SUV of the liver above 4.6. In addition, metabolically active lymph node and distant site involvement was indicative of significantly lower survival rates. On multivariate Cox regression analysis, the impact of intensity or SUV(max) of the primary tumor on outcome failed to attain significance, although PET performed better than some of the prognostic factors established in larger patient groups (P = 0.081)., Conclusion: (18)F-FDG PET/CT is a valuable tool for initial staging in children affected by rhabdomyosarcoma. (18)F-FDG PET/CT may be an additional predictor of outcome and may be used to refine risk-adapted therapy. PET performed better than some established risk factors. The borderline significance level of primary tumor metabolism in multivariate testing may be an effect of the limited sample size. Further prospective evaluations are warranted.

Unlabelled: Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) typically present with ventricular tachyarrhythmias preferentially triggered by an elevated sympathetic tone. Previous studies demonstrated an impairment of the presynaptic catecholamine reuptake as assessed by (123)I-labeled norepinephrine analog on metaiodobenzylguanidine ((123)I-MIBG) SPECT. Mutations in the gene encoding for plakophilin-2 (PKP-2) are the most common cause of autosomal dominant ARVC (ARVC-9). In this study, we investigated the potential role of adrenergic dysfunction on the arrhythmia profile in patients with ARVC and correlated these findings with the causative genotype., Methods: (123)I-MIBG SPECT was performed for 42 patients with definite ARVC (10 women, 32 men; mean age ± SD, 43 ± 14 y). Images were acquired at 4 h after injection and analyzed for regional (123)I-MIBG uptake in a standardized 33-segment polar map. Results were compared with those obtained from 10 control subjects (5 women, 5 men; mean age ± SD, 43 ± 12 y)., Results: An abnormal tracer uptake was detected in 25 patients with ARVC (59%). The extents of right ventricular dilation and regional wall motion abnormalities as well as electrocardiographic markers of de- or repolarization were not significantly different between patients with normal and abnormal (123)I-MIBG SPECT findings. However, during long-term follow-up of 11.9 ± 4.1 y, patients with abnormal (123)I-MIBG SPECT findings experienced life-threatening ventricular tachyarrhythmias significantly more often (22/25 patients [88%]) and independent of the extent of right ventricular dysfunction than those with a normal sympathetic innervation (6/17 patients [35%]; P < 0.0005). Mutations in PKP-2 were identified in 17 patients (40%) but were not correlated with the degree of adrenergic dysfunction., Conclusion: In patients with ARVC, an impairment of adrenergic innervation independent of the underlying genotype is associated with a higher incidence for future recurrences of ventricular tachyarrhythmias. This finding may suggest a potential role of (123)I-MIBG SPECT for individualized risk stratification in ARVC patients and asymptomatic PKP-2 mutation carriers alike.