Influence of the Molar Activity of [sup.203/212]Pb-PSC-PEG[sub.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 [[sup.177]Lu]Lu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-[Tyr[sup.3],Thr[sup.8]]-octreotide ([sup.177]Lu-DOTA-TOC) and, more recently, by a lead specific chelator (PSC) containing [sup.203/212]Pb-PSC-PEG[sub.2]-TOC (PSC-TOC). The molar activity (A[sub.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 [sup.203/212]Pb-PSC-TOC on cell uptake was investigated. (2) Methods: Optimized radiolabeling of [sup.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: [sup.203/212]Pb-PSC-TOC was radiolabeled with high radiochemical purity >95% and high radiochemical yield >95%, with A[sub.M] ranging from 0.2 to 61.6 MBq/nmol. The cell uptake of [sup.203]Pb-PSC-TOC (A[sub.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[sub.M]. (4) Conclusions: A moderate A[sub.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[sub.M] should be performed in the future. It was shown that A[sub.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[sub.M].