Biodistribution and radiation dosimetry of [18F]-JK-PSMA-7 as a novel prostate-specific membrane antigen-specific ligand for PET/CT imaging of prostate cancer

Abstract

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...

18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

“…For [ 18 F]CTT1057, comparable results have been reported (5.9 - 19.1). Uptake of [ 18 F]JK-PSMA-7 has also been found to be in the same range (12.8 ± 7.7) 32, 80. For the latter agent, the tumor-to-background ratios (with the gluteus muscle serving as reference) were significantly elevated, in particular in delayed scans 80 and such ratios would allow for a better comparison of the performance among all available radiotracers.…”

“…Regarding dosimetry, whole body doses similar to other radiotracers were reported, with a maximum in the kidneys. High uptake in suspicious lesions was found, increasing over time, suggesting benefits of a late start of the PET/CT acquisition 80. A pilot study in 10 patients who were examined with both PSMA-targeted radiotracers demonstrated that [ 18 F]JK-PSMA-7 was at least equivalent to [ 68 Ga]PSMA-11, as all [ 68 Ga]PSMA-11-positive lesions could be seen with [ 18 F]JK-PSMA-7 and several additional lesions were detected.…”

“…Clinical Investigations. In vivo data has been acquired in a first-in-human study as well as in a biodistribution and dosimetry study (n=10) 80, in a direct comparison with [ 68 Ga]PSMA-11 (n=10) and in clinical applications in a larger clinical population (n=124, Figure 6) 81. These studies demonstrate physiologic radiotracer accumulation in a pattern resembling the distribution known from other PSMA-targeted radiotracers with excretion via urinary and biliary pathways.…”

Discovery of 18F-JK-PSMA-7, a PET Probe for the Detection of Small PSMA-Positive Lesions

“…This study suggests promising performance with regard to detection of PSMA-positive tumor tissue. These clinical and dosimetry data were preliminarily presented at the 2018 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (28,29) and will be published in due course.…”

Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents

“…We have already used peripheral ganglia of healthy rats for the preclinical screening of novel PSMA ligands [24]. This study resulted in discovery of a PSMA PET probe with favorable imaging properties which is already used in clinic [25, 26]. However, a thorough characterization of the model is still lacking.…”