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

Karina Knorr; So Won Oh; Markus Krönke; Alexander Wurzer; Calogero D'Alessandria; Michael Herz; Wolfgang Weber; Hans-Jürgen Wester; Matthias Eiber; Nahid Yusufi; Stephan Nekolla

doi:10.1186/s13550-021-00872-w

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

EJNMMI Res. 2022 Feb 4;12(1):8. doi: 10.1186/s13550-021-00872-w.

Authors

Affiliations

¹ School of Medicine, Klinikum Rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany. karina.knorr@mri.tum.de.
² School of Medicine, Klinikum Rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany.
³ Department of Nuclear Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
⁴ School of Medicine, Klinikum Rechts der Isar, Department of Diagnostic and Interventional Radiology, Technical University of Munich, Munich, Germany.
⁵ Chair for Pharmaceutical Radiopharmacy, TUM, Garching, Germany.

^# Contributed equally.

Abstract

Background: Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands such as ¹⁸F-rhPSMA-7 are a new class of theranostic agents in clinical development for prostate cancer. We compared preclinical dosimetry and human biodistribution of ¹⁸F-rhPSMA-7 with that of single diastereoisomer form, ¹⁸F-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 ¹⁸F-rhPSMA-7 or 28.5 ± 4.8 MBq ¹⁸F-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. ¹⁸F-rhPSMA-7 (n = 47) and ¹⁸F-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 ¹⁸F-rhPSMA-7 versus ¹⁸F-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 ¹⁸F-rhPSMA-7 and 21.7 and 12.8 µSv/MBq for ¹⁸F-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 ¹⁸F-rhPSMA-7 versus ¹⁸F-rhPSMA-7.3, respectively. Tumour SUV_mean was higher for ¹⁸F-rhPSMA-7.3 (32.5 ± 42.7, n = 63 lesions) than for ¹⁸F-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. ¹⁸F-rhPSMA-7.3 showed significantly lower bladder uptake, and a higher uptake trend in tumours compared with ¹⁸F-rhPSMA-7.

Keywords: 18F; Biodistribution; Dosimetry; PET/CT; PSMA; rhPSMA.