Next Article in Journal
The Pluripotency Transcription Factor Oct4 Contributes to Head and Neck Squamous Cell Carcinoma Radioresistance via Regulation of DNA Repair and the Stem Cell Phenotype
Previous Article in Journal
Elucidating the Role of XRN2-Mediated DNA Repair Programs
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Abstract

The Cytotoxic Effect of 64Cu/NOTA-Terpyridine Platinum Conjugate, as a Novel Chemoradiotherapy Agent †

1
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
2
Sherbrooke Molecular Imaging Center (CIMS) of the CRCHUS, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada
*
Author to whom correspondence should be addressed.
Presented at the 1st International Electronic Conference on Cancers: Exploiting Cancer Vulnerability by Targeting the DNA Damage Response, 1–14 February 2021; Available online: https://iecc2021.sciforum.net/.
Med. Sci. Forum 2021, 3(1), 7; https://doi.org/10.3390/IECC2021-09220
Published: 31 January 2021

Abstract

:
Colorectal cancer is one of the most prevalent cancers worldwide that displays both intrinsic and acquired resistance to platinum-based chemotherapeutic agents (Pt-CAs). To overcome such resistance, new classes of Pt-CAs have been proposed, including terpyridine (TP) compounds that target the G-quadruplex tertiary structure of DNA. Additionally, recent studies indicate a maximum chemoradiation benefit when radiation is administered with Pt-CAs at their highest concentrations in cancer cell DNA. Accordingly, we synthesized a novel chemo-radiotheranostic agent by conjugating a TP moiety with 64Cu (64Cu-NOTA-TP). The in vitro cytotoxic effects, cellular uptake, internalization and efflux of 64Cu-NOTA-TP were measured for colorectal cancer (HCT116) and normal fibroblast (GM05757) cells. Radiolabeling NOTA-TP with 64Cu resulted in 17,530-, 40,083- and 66,000-fold enhancements in its cytotoxicity against HCT116 cells (EC50 = 0.017 ± 0.004, 0.012 ± 0.006 and 0.005 ± 0.0002 µM) as compared to coldCu-NOTA-terpyridine (EC50 = 298 ± 2, 481 ± 25 and 330 ± 51 µM) at 24, 48 and 72 h post-administration, respectively. More importantly, the cytotoxicity of the 64Cu-conjugate toward the HCT116 cells was about 3.8-fold higher than that of GM05757 cells at 24 and 72 h. This result was consistent with a 2–3-fold higher internalization of 64Cu-conjugate in HCT116 cells relative to GM05757 cells at similar times. The internalized activity of the 64Cu-conjugate steadily increased from 0.04 ± 0.02% to 18.7 ± 2.8% over a 24 h incubation time. Moreover, the efflux kinetics of the 64Cu-conjugate showed that more than 40% of internalized activity was retained by cancer cells over a 24 h period. In conclusion, this work presents a novel chemo-radiotherapeutic agent with considerable potential for targeted cancer treatment combined with radioisotope imaging.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/IECC2021-09220/s1.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Khosravifarsani, M.; Ait-Mohand, S.; Paquette, B.; Sanche, L.; Guérin, B. The Cytotoxic Effect of 64Cu/NOTA-Terpyridine Platinum Conjugate, as a Novel Chemoradiotherapy Agent. Med. Sci. Forum 2021, 3, 7. https://doi.org/10.3390/IECC2021-09220

AMA Style

Khosravifarsani M, Ait-Mohand S, Paquette B, Sanche L, Guérin B. The Cytotoxic Effect of 64Cu/NOTA-Terpyridine Platinum Conjugate, as a Novel Chemoradiotherapy Agent. Medical Sciences Forum. 2021; 3(1):7. https://doi.org/10.3390/IECC2021-09220

Chicago/Turabian Style

Khosravifarsani, Meysam, Samia Ait-Mohand, Benoit Paquette, Léon Sanche, and Brigitte Guérin. 2021. "The Cytotoxic Effect of 64Cu/NOTA-Terpyridine Platinum Conjugate, as a Novel Chemoradiotherapy Agent" Medical Sciences Forum 3, no. 1: 7. https://doi.org/10.3390/IECC2021-09220

APA Style

Khosravifarsani, M., Ait-Mohand, S., Paquette, B., Sanche, L., & Guérin, B. (2021). The Cytotoxic Effect of 64Cu/NOTA-Terpyridine Platinum Conjugate, as a Novel Chemoradiotherapy Agent. Medical Sciences Forum, 3(1), 7. https://doi.org/10.3390/IECC2021-09220

Article Metrics

Back to TopTop