F-Prostate-specific membrane antigen (PSMA)-1007 is mainly excreted through the liver. We benchmarked the performance of 18 F-PSMA-1007 against three renally excreted PSMA-tracers. Methods: Among 668 patients we selected 27 patients in whom the PET/CT with 68 Ga-PSMA-11, 18 F-DCFPyL, or 18 F-JK-PSMA-7 was interpreted as equivocal or negative or as oligometastatic disease (PET-1). Within <3 weeks, a second PET scan with 18 F-PSMA-1007 was performed (PET-2). The confidence in the interpretation of PSMA-positive loco-regional findings was scored on a 5-point scale, first in routine diagnostics (reader 1), then by an independent second evaluation (reader 2). Discordant PSMA-positive skeletal findings were examined by contrast enhanced MRI. Results: For both readers, 18 F-PSMA-1007 facilitated the interpretability of 27 loco-regional lesions. In PET-2, the clinical read-out led to a significantly lower number of equivocal loco-regional lesions (p=0.024), reader 2 reported a significantly higher rate of suspicious lesions that were falsely interpreted as probably benign in PET-1 (p=0.023). Exclusively on PET-2, we observed a total of 15 PSMA-positive PSMA-spots in the bone marrow of 6 patients (= 22%). None of the 15 discordant spots had a morphological correlate on the corresponding CT or on the subsequent MRI. Thus, 18 F-PSMA-1007 exhibits a significantly higher rate of unspecific medullary spots (p=0.0006). Conclusion: 18 F-PSMA-1007 may increase confidence to interpret small loco-regional lesions adjacent to the urinary tract. However, it may decrease the interpretability of skeletal lesions.

Absorbed organ doses of [(177)Lu]DKFZ-PSMA-617 therapy are not likely to be critical for kidneys, salivary glands, and the nasal mucous membrane. The lacrimal glands may represent the dose-limiting organs. Whole-body scintigraphy appears sufficient for dose estimation, but late measurements are mandatory, if accurate dose calculation is required.

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Aim We investigated the whole-body distribution and the radiation dosimetry of [ 18 F]-JK-PSMA-7, a novel 18 F-labeled PSMA-ligand for PET/CT imaging of prostate cancer. Methods Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329–384 MBq (mean 359 ± 17 MBq) [ 18 F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval. The kidneys, liver, lungs, spleen, and salivary glands were segmented into volumes of interest using the QDOSE dosimetry software suite (ABX-CRO, Germany). Absorbed and effective dose were calculated using the ICRP-endorsed IDAC 1.0 package. The absorbed dose of the salivary glands was determined using the spherical model of OLINDA 1.1. PSMA-positive lesions were evaluated separately. Quantitative assessment of the uptake in suspicious lesions was performed by analysis of maximum (max) and peak SUV values. The gluteus maximus muscle (SUV mean ) served as a reference region for the calculation of tumor-to-background ratios (TBR’s). Results Physiologic radiotracer accumulation was observed in the salivary and lacrimal glands, liver, spleen, and intestines, in a pattern resembling the distribution known from other PSMA-tracers with excretion via urinary and biliary pathways. The effective dose from [ 18 F]-JK-PSMA-7 for the whole body was calculated to be 1.09E−02 mGy/MBq. The highest radiation dose was observed in the kidneys (1.76E−01 mGy/MBq), followed by liver (7.61E−02 mGy/MBq), salivary glands (4.68E−02 mGy/MBq), spleen (1.89E−02 mGy/MBq), and lungs (1.10E-2 mGy/MBq). No adverse effects of tracer injection were observed. Six out of ten patients were scored as PSMA-positive. A total of 18 suspicious lesions were analyzed, which included six bone lesions, nine lymph nodes, and three local lesions within the prostate fossa. The values for the SUV max and SUV peak in the PSMA-positive lesions increased until 60 min p.i. and remained at this intensity in the PET/CT scans until 140 min. In the period between 170 and 200 min after injection, a further significant increase in SUV max and SUV peak within the PSMA-positive lesions was observed. Conclusions The highest TBR of [ 18 F]-JK-PSMA-7 was found 3 h after injection. From the kinetically collected data, it can be concluded that this trend may also continue in the further course. The start of the PET/CT acquisition should be chosen as late as possible. The high uptake in suspicious lesions in terms of absolute SUV max and relative TBR values indicates potentially high sensitivity of the tracer for d...

The short half-life of existing prostate-specific membrane antigen (PSMA) tracers limits their time for internalization into tumor cells after injection, which is an essential prerequisite for robust detection of tumor lesions with low PSMA expression on PET/CT scans. Due to its longer half-life, the 89 Zr-labeled ligand 89 Zr-PSMA-Df allows acquisition of PET scans up to 6 days after injection, thereby overcoming the above limitation. We investigated whether 89 Zr-PSMA-Df allowed more sensitive detection of weak PSMA-positive prostate cancer lesions. Methods:We selected 14 prostate cancer patients with biochemical recurrence who exhibited no PSMApositive lesions on a PET scan acquired with existing PSMA tracers ( 68 Ga-PSMA-11, 18 F-JK-PSMA-7).Within 5 weeks after the negative scan, we performed a second PSMA-PET scan using 89 Zr-PSMA-Df (117±16 MBq, PET acquisition within 6 days of injection).Results: 89 Zr-PSMA-Df detected 15 PSMA-positive lesions in 8/14 patients, who had a PET-negative reading of their initial PET scans with existing tracers. In these 8 patients, the new scans revealed localized recurrence of disease (3/8), metastases in lymph nodes (3/8), or lesions at distant sites (2/8).Based on these results, patients received lesion-targeted radiotherapies (5/8), androgen deprivation therapies (2/8), or no therapy (1/8). The plausibility of 14/15 lesions was supported by histology, clinical follow-up after radiotherapy or subsequent imaging. Furthermore, comparison of the 15 89 Zr-PSMA-Dfpositive lesions with their correlates on the original PET scan revealed that established tracers exhibited mild accumulation in 7/15 lesions but contrast-to-noise ratios (CNR) were too low for robust detection of these lesions (CNR 2.4±3.7 for established tracers vs. 10.2±8.5 for 89 Zr-PSMA-Df, p=0.0014). The SUVmax of the 15 89 Zr-PSMA-Df-positive lesions (11.5±5.8) was significantly higher than the SUVmax on the original PET scans (4.7±2.8, p=0.0001). Kidneys were the most exposed organ with doses of 3.3±0.7 mGy/MBq. The effective dose was 0.15±0.04 mSv/MBq. Conclusion:In patients with weak PSMA expression, a longer period of time might be needed for ligand internalization than that offered by existing PSMA tracers to make lesions visible on PET/CT scans.Hence, 89 Zr-PSMA-Df might be of significant benefit to patients in whom the search for weak PSMApositive lesions is challenging. Radiation exposure should be weighed against the potential benefit of metastasis-directed therapy or salvage radiotherapy, which we initiated in 36% (5/14) of our patients based on their 89 Zr-PSMA-Df PET scans.