Gadolinium and Platinum in Tandem: Real-time Multi-Modal Monitoring of Drug Delivery by MRI and Fluorescence Imaging

Hongguang Li¹, Bethany I. Harriss², Alkystis Phinikaridou³, Sara Lacerda³, Gregory Ramniceanu^5,6, Bich-Thuy Doan^5,6, Ka-Lok Ho¹, Chi-Fai Chan^1,4, Wai-Sum Lo⁴, René M. Botnar³, Rongfeng Lan¹, Cyrille Richard^5,6✉, Ga-Lai Law^4✉, Nicholas J. Long^2✉, Ka-Leung Wong^1✉

1. Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR;
2. Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom;
3. King's College London, Division of Imaging Sciences, Lambeth Wing, St Thomas' Hospital London SE1 7EH, United Kingdom;
4. Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR;
5. Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS); CNRS UMR 8258; Inserm U 1022; Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, 75006 Paris, France;
6. Chimie-ParisTech, PSL, 75005 Paris, France.

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Citation:
Li H, Harriss BI, Phinikaridou A, Lacerda S, Ramniceanu G, Doan BT, Ho KL, Chan CF, Lo WS, Botnar RM, Lan R, Richard C, Law GL, Long NJ, Wong KL. Gadolinium and Platinum in Tandem: Real-time Multi-Modal Monitoring of Drug Delivery by MRI and Fluorescence Imaging. Nanotheranostics 2017; 1(2):186-195. doi:10.7150/ntno.18619. Available from http://www.ntno.org/v01p0186.htm

Abstract

A novel dual-imaging cisplatin-carrying molecular cargo capable of performing simultaneous optical and MR imaging is reported herein. This long-lasting MRI contrast agent (r₁ relaxivity of 23.4 mM^-1s^-1 at 3T, 25 ^oC) is a photo-activated cisplatin prodrug (PtGdL) which enables real-time monitoring of anti-cancer efficacy. PtGdL is a model for monitoring the drug delivery and anti-cancer efficacy by MRI with a much longer retention time (24 hours) in several organs such as renal cortex and spleen than GdDOTA and its motif control GdL. Upon complete release of cisplatin, all PtGdL is converted to GdL enabling subsequent MRI analyses of therapy efficacy within its reasonably short clearance time of 4 hours. There is also responsive fluorescence enhancement for monitoring by photon-excitation.

Keywords: prodrug, multi-modal, MRI, drug delivery, fluorescence imaging, cisplatin.