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

EJNMMI Research

Hans-Jürgen Wester¹  Alexander Wurzer¹  Karina Knorr²  Matthias Eiber²  Wolfgang Weber²  Nahid Yusufi²  Stephan Nekolla²  Calogero D’Alessandria²  Michael Herz²  So Won Oh³  Markus Krönke⁴ 

[1] Chair for Pharmaceutical Radiopharmacy, TUM, Garching, Germany;School of Medicine, Klinikum Rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany;School of Medicine, Klinikum Rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany;Department of Nuclear Medicine, Seoul National University Boramae Medical Center, Seoul, Korea;School of Medicine, Klinikum Rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany;School of Medicine, Klinikum Rechts der Isar, Department of Diagnostic and Interventional Radiology, Technical University of Munich, Munich, Germany;

关键词: F;    Biodistribution;    Dosimetry;    PET/CT;    PSMA;    rhPSMA;   

DOI  :  10.1186/s13550-021-00872-w

来源: Springer

【 摘 要 】

BackgroundRadiohybrid 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.MethodsPreclinical 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. SUVmean 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.ResultsPreclinical 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; SUVmean 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 SUVmean 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).ConclusionsRadiation 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.

【 授权许可】

CC BY