Details

Autor(en) / Beteiligte

• Oh, So Won
• Wurzer, Alexander
• Yusufi, Nahid
• Nekolla, Stephan
• Herz, Michael
• Kropf, Saskia
• Weber, Wolfgang
• Wester, Hans
• Eiber, Matthias

Titel

Preclinical dosimetry and human biodistribution of 18F-rhPSMA-7 and 18F-rhPSMA-7.3

Ist Teil von

• The Journal of nuclear medicine (1978), 2019-05, Vol.60

Ort / Verlag

New York: Society of Nuclear Medicine

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Objectives: Prostate-specific membrane antigen (PSMA) targeting PET/CT imaging has been widely used for the diagnosis and therapy of prostate cancer. Radiohybrid PSMA (rhPSMA) ligands are a new class of theranostic agents that allow fast 18F synthesis and labelling with radiometals. rhPSMA-7 as its lead compound consists of four different isomers. From these isomers the enantiomeric pure rhPSMA-7.3 exhibits the most promising targeting characteristics for clinical translation. We compared the preclinical dosimetry and human biodistribution of 18F-rhPSMA-7 and 18F-rhPSMA-7.3. Methods: SCID-mice were injected and sacrificed at multiple time points at 10-300 min post-innjection(p.i.). 3-5 mice were injected per timepoint with a mean 25.6 ± 3.6 MBq of 18F-rhPSMA-7 and 28.5 ± 4.8 MBq of rhPSMA-7.3, respectively. Heart, lung, liver, spleen, pancreas, fat, stomach, small intestine, large intestine, kidney, muscle, bone, bladder, testicles, tail, and brain tissue was harvested, and urine and blood samples collected. Activities were measured in a well-counter and percentage of injected dose per gram (%ID/g) was calculated. OLINDA/EXM 1.0 was used to estimate the absorbed doses. Human biodistribution was estimated by analysing clinical 18F-rhPSMA-7- and 18F-rhPSMA-7.3-PET/CT exams in 47 and 32 patients, respectively. Mean injected activities were 324 (range 236-424) MBq vs. 345 (range 235-420) MBq and 84 (range 42-166) min and vs. 76 (range 59-122) min for 18F-rhPSMA-7 vs. 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 three representative tumor lesions. Results: Preclinical dosimetry revealed that using 3.5h and 1h bladder voiding interval the extrapolated total effective doses were 2.66E-02 and 1.22E-02 mSv/MBq for 18F-rhPSMA-7, and 2.17E-02 and 1.28E-02 mSv/MBq for 18F-rhPSMA-7.3, respectively. Human biodistribution of 18F-rhPSMA-7 and 18F-rhPSMA-7.3 showed the typical pattern known from other PSMA-ligands. Uptake parameters for 18F-rhPSMA-7 and 18F-rhPSMA-7.3 were very similar with a trend towards lower renal uptake and activity retention in the bladder for 18F-rhPSMA-7.3: SUVmean were 16.9 vs. 16.0 (parotid gland), 19.6 vs. 19.6 (submandibular gland), 2.0 vs. 1.9 (blood pool), 0.7 vs. 0.7 (lungs), 7.0 vs. 7.3 (liver), 9.1 vs. 8.5 (spleen), 55.2vs.35.5 (kidney), 2.5 vs. 2.9 (pancreas), 10.9 vs. 11.0 (duodenum), 1.1 vs. 1.3 (non-diseased bone) and 10.2 vs. 2.0 (bladder) for 18F-rhPSMA-7 vs. 18F-rhPSMA-7.3, respectively. In particular, uptake values of 18F-rhPSMA-7.3 PET/CT were significantly lower in the kidney (35.5 ± 9. 8 vs. 55.2 ± 22.7, p<0.001) and bladder (2.0 ± 0.8 vs. 10.2 ± 21.2, p <0.001). Tumor uptake was analyzed in 89 lesions (26 primary tumors/local recurrences, 23 bone, 38 lymph node and 2 visceral metastases) and 63 lesions (14 primary tumors/local recurrences, 30 bone, 18 lymph node and 1 visceral metastases) for 18F-rhPSMA-7 and 18F-rhPSMA-7.3, respectively. SUVmean of tumor lesions was significantly higher for 18F-rhPSMA-7.3 (20.0 ± 20.2 vs. 32.5 ± 42.7, p <0.001). Conclusions: Radiation dosimetry is favourable both for 18F-rhPSMA-7 and 18F-rhPSMA-7.3 and radiation exposure assuming a 1h voiding interval is less than 5 mSv after injection of 370 MBq. Human biodistribution is similar with a trend towards lower kidney uptake and activity retention in the bladder and a higher uptake in tumor lesions of 18F-rhPSMA-7.3.