Year: 2026
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide DOTA-radiometal (DOTA: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) hapten complexes of β-emitters ( 177 Lu or 90 Y) and α-emitters ( 225 Ac) can be selectively targeted to tumors using an antitumor/anti-DOTA bispecific antibody (BsAb) approach in pretargeted radioimmunotherapy (DOTA-PRIT). Clinical translation of DOTA-PRIT may be accelerated by the development of a 68 Ga companion diagnostic for PET imaging. Here, we report a novel radiohapten, which uses a 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) chelator for 68 Ga labeling while retaining 175 Lu in a benzyl-DOTA moiety for high-affinity antibody recognition (NODAGA-Pr; Pr = Proteus). Radiolabeling of NODAGA-Pr with 68 Ga showed high radiochemical yield and purity, and in vitro studies confirmed high radiostability and negligible serum-protein binding. In vivo, using a DOTA-PRIT system targeting the GPA33 antigen in a human colorectal cancer mouse model, [ 68 Ga]Ga-NODAGA-Pr demonstrated efficient tumor uptake and high-contrast PET imaging. Additional studies using an established DOTA-hapten test system─human embryonic kidney 293T cells expressing a transmembrane-anchored anti-DOTA scFv huC825 further confirmed its in vivo PRIT performance. These findings support [ 68 Ga]Ga-NODAGA-Pr as a promising agent for pretargeted immunoPET and for imaging engineered cells expressing a radiohapten capture reporter gene, with favorable pharmacokinetics and tumor targeting well matched to existing therapeutic DOTA-radiohaptens.
Source: Molecular Pharmaceutics
Authors: Darren R. Veach, Daniela Burnes Vargas, Baharul Islam, Sang Gyu Lee, Leah Gajecki, Brett A. Vaughn, Guangbin Yang, Teja Muralidhar Kalidindi, Naga Vara Kishore Pillarsetty, Niloufar Salehi, Ambika P. Jaswal, Sayani Saha, Alexandre B. Le Roux, Hong Xu, Hong-fen Guo, Ouathek Ouerfelli, Nai-Kong V. Cheung, Simone Krebs, Steven M. Larson, Sarah M. Cheal
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1463316280, G2051006376, G289723095, G5065492887, G526170626, DOTA-based pre-targeting of alpha emitters, Organic Synthesis at the Service of Biology and Medicine, MSKCC Center for Molecular Imaging in Cancer, G9000003249, Cancer Center Support Grant, IL13Ra2-targeted radioimmunotherapy for glioblastoma, SPORE in Brain Cancer, Interrogating the in vivo pharmacokinetics of armored CARs with radiohapten capture
OpenAlex ID: W7161627263