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

Meysam Khosravifarsani; Samia Ait-Mohand; Benoit Paquette; Léon Sanche; Brigitte Guérin

doi:10.3389/fmed.2022.975213

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

Front Med (Lausanne). 2022 Sep 23:9:975213. doi: 10.3389/fmed.2022.975213. eCollection 2022.

Authors

Meysam Khosravifarsani¹, Samia Ait-Mohand¹, Benoit Paquette¹, Léon Sanche¹, Brigitte Guérin^{1

2}

Affiliations

¹ Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
² Sherbrooke Molecular Imaging Center (CIMS), Centre de Recherche du CHUS (CRCHUS), Université de Sherbrooke, Sherbrooke, QC, Canada.

Abstract

To overcome resistance to chemotherapy for colorectal cancer, we propose to validate in vivo a novel terpyridine-platinum (TP) compound radiolabeled with the radio-theranostic isotope ⁶⁴Cu. In vivo stability, biodistribution, PET imaging, tumor growth delay, toxicity and dosimetry of [⁶⁴Cu]NOTA-C3-TP were determined. The current experimental studies show that [⁶⁴Cu]NOTA-C3-TP is stable in vivo, 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. [⁶⁴Cu]NOTA-C3-TP retarded tumor growth by up to 6 ± 2.0 days and improved survival relative to vehicle and non-radioactive [^NatCu]NOTA-C3-TP over 17 days of tumor growth observation. This effect was obtained with only 0.4 nmol i.v. injection of [⁶⁴Cu]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 [⁶⁴Cu]NOTA-TP as a novel radio-theranostic agent.

Keywords: colorectal cancer; copper-64; radio-theranostic agent; resistance; terpyridine platinum complexes.