Preclinical biodistribution and dosimetry and human biodistribution comparing (18)F-rhPSMA-7 and single isomer (18)F-rhPSMA-7.3

BACKGROUND: Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands such as (18)F-rhPSMA-7 are a new class of theranostic agents in clinical development for prostate cancer. We compared preclinical dosimetry and human biodistribution of (18)F-rhPSMA-7 with that of single diastereoisomer form, (18)F-rhPSMA-7.3. METHODS: Preclinical dosimetry was performed with SCID-mice sacrificed at multiple timepoints (10–300 min) post-injection of 25.6 ± 3.6 MBq (18)F-rhPSMA-7 or 28.5 ± 4.8 MBq (18)F-rhPSMA-7.3 (n = 3–6 mice per timepoint). Heart, lung, liver, spleen, pancreas, fat, stomach, small intestine, large intestine, kidney, muscle, bone, bladder, testicles, tail, and brain tissue were harvested, and urine and blood samples collected. Percentage of injected dose per gram was calculated. Absorbed doses were estimated with OLINDA/EXM 1.0. (18)F-rhPSMA-7 (n = 47) and (18)F-rhPSMA-7.3 (n = 33) PET/CT exams were used to estimate human biodistribution. Mean (range) injected activities were 324 (236–424) MBq versus 345 (235–420) MBq, and acquisition times were 84 (42–166) versus 76 (59–122) minutes for (18)F-rhPSMA-7 versus (18)F-rhPSMA-7.3, respectively. SUV(mean) was determined for background (gluteal muscle), normal organs (salivary glands, blood pool, lung, liver, spleen, pancreas, duodenum, kidney, bladder, bone) and up to three representative tumour lesions. Qualitative analyses assessed image quality, non-specific blood pool activity, and background uptake in bone/marrow using 3/4-point scales. RESULTS: Preclinical dosimetry revealed that at 3.5 h and 1 h bladder voiding intervals, the extrapolated total effective doses were 26.6 and 12.2 µSv/MBq for (18)F-rhPSMA-7 and 21.7 and 12.8 µSv/MBq for (18)F-rhPSMA-7.3 respectively. Human biodistribution of both agents was typical of other PSMA-ligands and broadly similar to each other; SUV(mean) were 16.9 versus 16.2 (parotid gland), 19.6 versus 19.9 (submandibular gland), 2.0 versus 1.9 (blood pool, p < 0.005), 0.7 versus 0.7 (lungs), 7.0 versus 7.3 (liver), 9.1 versus 8.4 (spleen), 32.4 versus 35.7 (kidney), 2.5 versus 2.8 (pancreas), 10.9 versus 11.0 (duodenum), 1.1 versus 1.3 (bone) and 4.6 versus 2.0 (bladder; p < 0.001) for (18)F-rhPSMA-7 versus (18)F-rhPSMA-7.3, respectively. Tumour SUV(mean) was higher for (18)F-rhPSMA-7.3 (32.5 ± 42.7, n = 63 lesions) than for (18)F-rhPSMA-7 (20.0 ± 20.2, n = 89 lesions). CONCLUSIONS: Radiation dosimetry is favourable for both agents. Radiation exposure, assuming a 1 h voiding interval, is less than 5 mSv after injection of 370 MBq. (18)F-rhPSMA-7.3 showed significantly lower bladder uptake, and a higher uptake trend in tumours compared with (18)F-rhPSMA-7. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-021-00872-w.