177 Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castrationresistant 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.
Background-Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular functionafter experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs. Methods and Results-Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [ 111 In]indium oxine. EPCs (10 6 ) were injected in athymic nude rats 24 hours after myocardial infarction (nϭ8) or sham operation (nϭ8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, Ϸ70% of the radioactivity was localized in the spleen and liver, with only Ϸ1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02Ϯ0.19 in sham-operated animals to 2.03Ϯ0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69Ϯ1.54 in sham-operated animals to 4.70Ϯ1.55 (PϽ0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone. Conclusions-Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy. (Circulation.
Background-Clinical trials indicate a beneficial effect of intracoronary infusion of progenitor cells on myocardial function in patients with ischemic heart disease. The extent and potential determinants of proangiogenic progenitor cell homing into the damaged myocardium after intracoronary infusion and the underlying mechanisms are still unknown. Method and Results-Circulating proangiogenic progenitor cells isolated from peripheral blood and cultivated for 3 days were labeled with radioactive indium oxine ( 111 In-oxine). Radiolabeled proangiogenic progenitor cells (7.6Ϯ3.0 MBq, meanϮSD) were administered to patients with previous myocardial infarction and a revascularized infarct vessel at various stages after infarction (5 days to 17 years). Viability of the infarcted myocardium was determined by 18 F-fluorodeoxyglucose-positron emission tomography and microcirculatory function by intracoronary Doppler measurements. One hour after application of progenitor cells, a mean of 6.9Ϯ4.7% (range, 1% to 19%; nϭ17) of total radioactivity was detected in the heart, which declined to 2Ϯ1% after 3 to 4 days. Average activity within the first 24 hours was highest among patients with acute myocardial infarction (Յ14 days; 6.3Ϯ2.9%; nϭ8) and progressively decreased in patients treated in an intermediate phase (Ͼ14 days to 1 year; 4.5Ϯ3.2%; nϭ4) or a chronic stage (infarct age Ͼ1 year; 2.5Ϯ1.6%; nϭ5). Low viability of the infarcted myocardium and reduced coronary flow reserve were significant (PϽ0.05) predictors of proangiogenic progenitor cell homing. Conclusions-In patients after myocardial infarction undergoing intracoronary infusion of111 In-oxine-labeled proangiogenic progenitor cells, a substantial amount of radioactivity is detected for several days in the heart, indicating homing of progenitor cells to the myocardium. The amount of proangiogenic progenitor cells retained in the heart decreased progressively with time after the acute myocardial infarction. Proangiogenic progenitor cells preferentially home to extensive acute myocardial infarcts characterized by low viability and reduced coronary flow reserve. (Circulation.
FDG-PET allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after each cycle of chemotherapy. Moreover, relative changes in SUV after the first and second cycle are a strong predictor of response. Thus, FDG-PET may be helpful for individual treatment stratification in breast cancer patients.
Ga-labeled prostate-specific membrane antigen (Ga-PSMA) PET/CT has a proven role in staging and restaging of prostate cancer (PCA). The aims of this study were to evaluate the association of intraprostatic Ga-PSMA PET/CT findings and PSMA expression in immunohistochemical staining and generate a cutoff value for differentiation between normal prostate (PN) and PCA. The data of 31 patients (mean age, 67.2 y) who underwent prostatectomy and preoperative PET were retrospectively analyzed. On PET, focally increased uptake in the prostate was suggestive of tumor. A region of interest was placed on the suggestive area to generate an SUV; a similar region of interest was placed on adjacent visually PN. Both PCA and PN were stained with monoclonal anti-PSMA antibody (clone 3E6, 1:100, M3620). All intraprostatic PCA lesions on PET could be confirmed histopathologically. In PN sections ( = 31), median staining intensity was mild, median percentage of stained cells was 20% ± 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections ( = 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% ± 16.46%. The mean SUV (±SD) of PCA (14.06 ± 15.56) was significantly higher than that of PN (2.43 ± 0.63; < 0.001). Receiver-operating-characteristic curve analyses of the SUV of PCA, validated by immunohistochemical staining in 62 tissue samples, showed the best cutoff to be 3.15 (sensitivity, 97%; specificity, 90%; area under curve, 0.987). Applied to multifocal PCA, it resulted in sensitivity and specificity of 87% and 97% respectively. The mean SUV of PCA and PN for an IRS of less than 2 ( = 26; 2.52 ± 0.64) was significantly lower than the mean SUV for an IRS of 2 or more ( = 36; 12.38 ± 15.02; < 0.001). The mean SUV was significantly lower in PCA samples with fewer than 50% stained cells ( = 30; 2.81 ± 2.35) than in samples with 50% or more ( = 32; 13.34 ± 15.55; < 0.001). There was no correlation between the SUV of PCA and Gleason score ( = 0.54). This study showed that SUV on Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.
The serum detection of S100B, a new melanoma marker, has shown clinical significance in early studies. The aim of our study of 1,339 serum samples from 412 different melanoma patients and 107 control patients was to prove the prognostic value of serum S100B levels in melanoma patients at different stages of disease and at follow-up (median: 30 months). Using a cutoff level of 0.2 μg/l S100B, 5 of 286 patients (1.7%) with primary tumors (stage I/II), 14/73 (19.2%) patients with locoregional metastasis (stage III) and 57/84 (67.9%) patients with advanced disease (stage IV) were S100B positive (statistically significant differences for stage I/II vs. III, I/II vs. IV, and III vs. IV, p < 0.001). The estimated overall survival time was significantly longer (p < 0.001) for patients with S100B values below 0.2 μg/l compared to patients with elevated S100B levels (≥0.2 μg/l), which was independent of the stage of disease (I–IV). Regarding prognosis, we were furthermore able to distinguish different subgroups among stage III and IV patients using S100B serum levels (p < 0.01). Patients with different cutaneous non-melanoma diseases served as S100B-negative controls. S100B serum evaluations using the Sangtec®100 IRMA are highly specific and sensitive for the detection of metastatic melanoma. S100B has been shown to be a relevant prognostic factor for survival in a study with a large sample size of melanoma patients including close follow-up evaluations.
In breast cancer, FDG-PET is superior to conventional imaging procedures for detection of distant metastases. Although FDG-PET and CT provided similar diagnostic accuracy, the information was often found to be complementary. With increasing availability of FDG-PET/CT, prospective studies are needed to determine whether it could potentially replace the array of conventional imaging procedures used today.
This biodistribution study provided a broad range of uptake data of [(68)Ga]PSMA-11 for normal organs/tissues, primary prostate tumours and metastatic lesions based on a large patient cohort. Both PT and small metastatic lesions were detectable due to their high tracer uptake. Four-times-higher median uptake in PT in comparison to normal prostate stroma resulted in a high diagnostic accuracy that could potentially be used for multimodal image-guided biopsy with dedicated reconstruction software.
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