AUTHOR=Khosravifarsani Meysam , Ait-Mohand Samia , Paquette Benoit , Sanche Léon , Guérin Brigitte 

TITLE=In vivo behavior of [64Cu]NOTA-terpyridine platinum, a novel chemo-radio-theranostic agent for imaging, and therapy of colorectal cancer

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.975213

DOI=10.3389/fmed.2022.975213

ISSN=2296-858X

ABSTRACT=<p>To overcome resistance to chemotherapy for colorectal cancer, we propose to validate <italic>in vivo</italic> a novel terpyridine-platinum (TP) compound radiolabeled with the radio-theranostic isotope <sup>64</sup>Cu. <italic>In vivo</italic> stability, biodistribution, PET imaging, tumor growth delay, toxicity and dosimetry of [<sup>64</sup>Cu]NOTA-C3-TP were determined. The current experimental studies show that [<sup>64</sup>Cu]NOTA-C3-TP is stable <italic>in vivo</italic>, rapidly eliminated by the kidneys and has a promising tumor uptake ranging from 1.8 ± 0.4 to 3.0 ± 0.2 %ID/g over 48 h. [<sup>64</sup>Cu]NOTA-C3-TP retarded tumor growth by up to 6 ± 2.0 days and improved survival relative to vehicle and non-radioactive [<sup>Nat</sup>Cu]NOTA-C3-TP over 17 days of tumor growth observation. This effect was obtained with only 0.4 nmol <italic>i.v</italic>. injection of [<sup>64</sup>Cu]NOTA-C3-TP, which delivers 3.4 ± 0.3 Gy tumoral absorbed dose. No evidence of toxicity, by weight loss or mortality was revealed. These findings confirm the high potential of [<sup>64</sup>Cu]NOTA-TP as a novel radio-theranostic agent.</p>