Influence of the Molar Activity of 203/212 Pb-PSC-PEG 2 -TOC on Somatostatin Receptor Type 2-Binding and Cell Uptake.

(1) Background: In neuroendocrine tumors (NETs), somatostatin receptor subtype 2 is highly expressed, which can be targeted by a radioactive ligand such as [ 177 Lu]Lu-1,4,7,10-tetraazacyclododecane- N , N ', N ″, N ‴,-tetraacetic acid-[Tyr 3 ,Thr 8 ]-octreotide ( 177 Lu-DOTA-TOC) and, more recently, by a lead specific chelator (PSC) containing 203/212 Pb-PSC-PEG 2 -TOC (PSC-TOC). The molar activity (A M ) can play a crucial role in tumor uptake, especially in receptor-mediated uptake, such as in NETs. Therefore, an investigation of the influence of different molar activities of 203/212 Pb-PSC-TOC on cell uptake was investigated. (2) Methods: Optimized radiolabeling of 203/212 Pb-PSC-TOC was performed with 50 µg of precursor in a NaAc/AcOH buffer at pH 5.3-5.5 within 15-45 min at 95° C. Cell uptake was studied in AR42 J, HEK293 sst2, and ZR75-1 cells. (3) Results: 203/212 Pb-PSC-TOC was radiolabeled with high radiochemical purity >95% and high radiochemical yield >95%, with A M ranging from 0.2 to 61.6 MBq/nmol. The cell uptake of 203 Pb-PSC-TOC (A M = 38 MBq/nmol) was highest in AR42 J (17.9%), moderate in HEK293 sstr (9.1%) and lowest in ZR75-1 (0.6%). Cell uptake increased with the level of A M . (4) Conclusions: A moderate A M of 15-40 MBq/nmol showed the highest cell uptake. No uptake limitation was found in the first 24-48 h. Further escalation experiments with even higher A M should be performed in the future. It was shown that A M plays an important role because of its direct dependence on the cellular uptake levels, possibly due to less receptor saturation with non-radioactive ligands at higher A M .