Radiation dosimetry for 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer: Absorbed dose in normal organs and tumor lesions

Prostate-specific membrane antigen (PSMA) targeted radioligand therapy (RLT) is increasingly used in metastatic castration-resistant prostate cancer (mCRPC). We aimed to estimate the absorbed doses for normal organs and tumor lesions using (177)Lu-PSMA-I&T in patients undergoing up to four cycles RLT. Results were compared to pre-therapeutic (68)Ga-PSMA-HBED-CC positron-emission-tomography (PET).

A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 minutes, 24 hours and 6-8 days after administration. Regions of interest (ROIs) covering the whole body, organs and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pre-therapeutic (68)Ga-PSMA-HBED-CC PET/Computed tomography (CT). Absorbed doses for individual cycles were calculated using OLINDA/EXM. Standardized-uptake-values (SUV) from pre-therapeutic PET were compared to absorbed doses and to change of SUV.

Mean whole body effective dose for all cycles was 0.06±0.03 Sv/GBq. The mean absorbed organ doses were 0.72±0.21 Gy/GBq for the kidneys, 0.12±0.06 Gy/GBq for liver, 0.55±0.14 Gy/GBq for parotid, 0.64±0.40 Gy/GBq for the submandibular and 3.8±1.4 Gy/GBq for lacrimal glands. Absorbed organ doses were relatively constant when among the four different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2±2.6 Gy/GBq (range 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased with 3.5±2.9 Gy/GBq for the first, 3.3±2.5 Gy/GBq for the second, 2.7±2.3 Gy/GBq for the third and 2.4±2.2 Gy/GBq for the fourth cycle. SUVs of pre-therapeutic PET moderately correlated with absorbed dose (r=0.44, p<0.001 for SUVmax, r=0.43, p<0.001 for SUVmean) and moderately correlated with the change of SUV (ΔSUV; r=0.478, p<0.001 for SUVmax, r=0.50, p<0.001 for SUVmean).

Organ and tumor absorbed doses for (177)Lu-PSMA-I&T are comparable to recent reports and complement these with information on an excellent correlation between the four therapy cycles. With the kidneys representing the critical organ, a cumulative activity of 40 GBq (177)Lu-PSMA-I&T appears to be safe and justifiable. The correlation between pre-therapeutic SUV and absorbed tumor dose emphasizes the need for PSMA-ligand PET-imaging for patient selection.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 Sep 22 [Epub ahead of print]

Shozo Okamoto, Anne Thieme, Jakob Allmann, Calogero D'Alessandria, Tobias Maurer, Margitta Retz, Robert Tauber, Matthias M Heck, Hans-Juergen Wester, Nagara Tamaki, Wolfgang P Fendlder, Ken Herrmann, Christian H Pfob, Klemens Scheidhauer, Markus Schwaiger, Sibylle Ziegler, Matthias Eiber

Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Japan;, Department of Urology, Klinikum Rechts der Isar, Technical University of Munich;, Chair of Pharmaceutical Radiochemistry, Technical University of Munich, Germany;, Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine;, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angel.

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