Influence of the Molar Activity of 203/212Pb-PSC-PEG2-TOC on Somatostatin Receptor Type 2-Binding and Cell Uptake

Marc Pretze; Enrico Michler; Roswitha Runge; Kerstin Wetzig; Katja Tietze; Florian Brandt; Michael K. Schultz; Jörg Kotzerke

doi:10.3390/ph16111605

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Influence of the Molar Activity of 203/212Pb-PSC-PEG2-TOC on Somatostatin Receptor Type 2-Binding and Cell Uptake

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Influence of the Molar Activity of 203/212Pb-PSC-PEG2-TOC on Somatostatin Receptor Type 2-Binding and Cell Uptake

Marc Pretze, Enrico Michler, Roswitha Runge, Kerstin Wetzig, Katja Tietze, Florian Brandt, Michael K. Schultz and Jörg Kotzerke

Pharmaceuticals (Basel, Switzerland), Vol.16(11), 1605

11/14/2023

DOI: 10.3390/ph16111605

PMCID: PMC10675797

PMID: 38004470

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Abstract

(1) Background: In neuroendocrine tumors (NETs), somatostatin receptor subtype 2 is highly expressed, which can be targeted by a radioactive ligand such as [177Lu]Lu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴,-tetraacetic acid-[Tyr3,Thr8]-octreotide (177Lu-DOTA-TOC) and, more recently, by a lead specific chelator (PSC) containing 203/212Pb-PSC-PEG2-TOC (PSC-TOC). The molar activity (AM) 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 203/212Pb-PSC-TOC on cell uptake was investigated. (2) Methods: Optimized radiolabeling of 203/212Pb-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: 203/212Pb-PSC-TOC was radiolabeled with high radiochemical purity >95% and high radiochemical yield >95%, with AM ranging from 0.2 to 61.6 MBq/nmol. The cell uptake of 203Pb-PSC-TOC (AM = 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 AM. (4) Conclusions: A moderate AM 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 AM should be performed in the future. It was shown that AM 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 AM.

Details

Title: Subtitle: Influence of the Molar Activity of 203/212Pb-PSC-PEG2-TOC on Somatostatin Receptor Type 2-Binding and Cell Uptake
Creators: Marc Pretze - University Hospital Carl Gustav Carus
Enrico Michler - University Hospital Carl Gustav Carus
Roswitha Runge - University Hospital Carl Gustav Carus
Kerstin Wetzig - University Hospital Carl Gustav Carus
Katja Tietze - University Hospital Carl Gustav Carus
Florian Brandt - University Hospital Carl Gustav Carus
Michael K. Schultz - Viewpoint Molecular Targeting (United States)
Jörg Kotzerke - University Hospital Carl Gustav Carus
Resource Type: Journal article
Publication Details: Pharmaceuticals (Basel, Switzerland), Vol.16(11), 1605
DOI: 10.3390/ph16111605
PMID: 38004470
PMCID: PMC10675797
NLM abbreviation: Pharmaceuticals (Basel)
ISSN: 1424-8247
eISSN: 1424-8247
Language: English
Date published: 11/14/2023
Academic Unit: Radiology; Radiation Oncology
Record Identifier: 9984512058002771

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