PT  - JOURNAL ARTICLE
AU  - Kalidindi, Teja Muralidhar
AU  - Lee, Sang Gyu
AU  - Punzalan, Blesida
AU  - Veach, Darren
AU  - Jou, Katerina
AU  - Chakraborty, Goutam
AU  - Tagawa, Scott
AU  - Bander, Neil
AU  - Lewis, Jason
AU  - Larson, Steven
AU  - Osborne, Joseph
AU  - Pillarsetty, NagaVaraKishore
TI  - Effect of reducing specific activity of [<sup>177</sup>Lu]-DKFZ-PSMA617 on uptake in the tumor, salivary gland and kidney
DP  - 2020 May 01
TA  - Journal of Nuclear Medicine
PG  - 230--230
VI  - 61
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/61/supplement_1/230.short
4100  - http://jnm.snmjournals.org/content/61/supplement_1/230.full
SO  - J Nucl Med2020 May 01; 61
AB  - 230Objectives: Peptide based radiotherapeutic agents targeting prostate specific membrane antigen (PSMA) such [177Lu]-DKFZ-PSMA617 ([177Lu]-PSMA617), [177Lu]-PSMA-I&T, [131I]-MIP-1095, [225Ac]-DKFZ-PSMA617 have emerged as leading candidates for treating metastatic castration resistant prostate cancer. Patients undergoing therapies with [177Lu]-PSMA617 or [225Ac]-PSMA617 have experienced high grade xerostomia and medium to low grade nephropathy arising due to salivary gland and kidney toxicity. Using [68Ga]-PSMA11 we demonstrated that by lowering apparent specific activity (ASA) we observed significant reduction in renal uptake without affecting the tumor uptake (1). Here in we present our data on the effect of reducing ASA of [177Lu]-PSMA617 on the tumor, salivary gland and kidney uptake. Methods: [177Lu]-PSMA617 was synthesized using established protocol and the apparent specific activity of the product was varied by adding cold ligand DKFZ-PSMA11. Athymic nude mice (n=20) bearing PC3-PIP (PSMA+) tumor xenografts were administered 277 kBq (7.5 µCi) of [177Lu]-PSMA617 at ASA’s of 0.3, 0.15, 0.03, 0.007, 0.0036 and 0.0018 mCi/nmol. Terminal biodistribution studies were conducted 1 h post administration to determine mean uptake in organs (%ID/g). Results: Biodistribution studies revealed that [177Lu]-PSMA617 uptake in PC3-PIP tumors were 21.83±6.21, 18.7±2.01, 26.52±2.9, 16.17±3.7, 13.52±3.68, and 12.18±1.68 %ID/g at ASA’s of 0.3, 0.15, 0.03, 0.007 and 0.0036 and 0.0018 mCi/nmol respectively. Corresponding kidney uptake values were 123.14±52.52, 132.31±47.4, 84.29±78.25, 2.189±1.85, 1.16±0.36, 0.65±0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.57±0.16, 0.45±0.15, 0.41±0.3, 0.11±0.03, 0.23±0.23, 0.08±0.03 % ID/g, respectively. Conclusions: These studies establish that salivary gland and kidney uptake can be drastically reduced without affecting tumor uptake of 177Lu-PSMA617 simply by reducing its specific activity. These studies provide proof of concept solutions for xerostomia and renal toxicity arising from [177Lu]-PSMA617. References: Pillarsetty N, et al. J Nucl Med 2016 vol. 57 (supplement_2), 528.