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. 2022 Feb 4;12(1):8.
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

Karina Knorr  1 , So Won Oh  2   3 , Markus Krönke  2   4 , Alexander Wurzer  5 , Calogero D'Alessandria  2 , Michael Herz  2 , Wolfgang Weber  2 , Hans-Jürgen Wester  5 , Matthias Eiber  2 , Nahid Yusufi #  2 , Stephan Nekolla #  2
Affiliations

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

Karina Knorr et al. EJNMMI Res. .

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. 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.

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; 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).

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.

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Conflict of interest statement

Patent application for rhPSMA (HJW, AW and ME). HJW and ME received funding from the SFB 824 (DFG Sonderforschungsbereich 824, Project B11) from the Deutsche Forschungsgemeinschaft, Bonn, Germany and Blue Earth Diagnostics Limited (licensee for rhPSMA) as part of an academic collaboration. HJW is founder, shareholder and advisor board member of Scintomics GmbH, Fuerstenfeldbruck, Germany. WW is a consultant for Blue Earth Diagnostics Limited. ME reports prior consulting activities for Blue Earth Diagnostics, Progenics Pharmaceuticals, Point Biopharma and Janssen Pharmaceuticals. No other potential conflicts of interest relevant to this article exist.

Figures

Fig. 1
Fig. 1
Human biodistribution in normal organs and tumours of 18F-rhPMSA-7 (A) and 18F-rhPSMA-7.3 using SUVmean. SMG: submandibular gland
Fig. 2
Fig. 2
Maximum intensity projection images of patients with normal biodistribution of 18F-rhPSMA-7 (A) and 18F-rhPSMA-7.3 (B), respectively
See this image and copyright information in PMC

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