Pretargeted radioimmunotherapy and SPECT imaging of peritoneal carcinomatosis using bioorthogonal click chemistry: probe selection and first proof-of-concept.

ABSTRACT: Rationale : Pretargeted radioimmunotherapy (PRIT) based upon bioorthogonal click chemistry has been investigated for the first time in the context of peritoneal carcinomatosis using a CEA-targeting 35A7 mAb bearing trans-cyclooctene (TCO) moieties and several ¹⁷⁷Lu-labeled tetrazine (Tz) radioligands. Starting from three Tz probes containing PEG linkers of varying lengths between the DOTA and Tz groups (i.e. PEG_n = 3, 7, or 11, respectively, for Tz-1, Tz-2, and Tz-3), we selected [¹⁷⁷Lu]Lu-Tz-2 as the most appropriate for pretargeted SPECT imaging and demonstrated its efficacy in tumor growth control. Methods: An orthotopic model of peritoneal carcinomatosis (PC) was obtained following th

SUBMITTER: Rondon A 

PROVIDER: S-EPMC6771248 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature