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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Subhajit Ghosh, Tapas Das*, Shishu K. Suman, Haladhar D. Sarma and Ashutosh Dash

DOI: 10.2174/1871520620666200502002609

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Preparation and Preliminary Evaluation of 68Ga-Acridine: An Attempt to Study the Potential of Radiolabeled DNA Intercalator as a PET Radiotracer for Tumor Imaging

Page: [1538 - 1547] Pages: 10

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Abstract

Introduction: Acridine is a well-known DNA intercalator and thereby gets easily inserted within DNA. As uncontrolled rapid cell division is one of the primary characteristics of the tumors, it is expected that acridine or its suitable derivatives will have preferential accumulation in the tumorous lesions. Therefore, an attempt was made to radiolabel an acridine derivative with 68Ga and study the potential of the 68Ga-acridine complex as a PET agent for tumor imaging.

Methods: 9-aminoacridine was coupled with p-NCS-benzyl-DOTA to render it suitable for labeling with 68Ga. The purified acridine-DOTA conjugate was radiolabeled with 68Ga, eluted from a 68Ge/68Ga radionuclide generator. Various radiolabeling parameters were optimized and the stability of the radiolabeled preparation was studied. The biological behavior of the 68Ga-acridine complex was studied both in vitro and in vivo using Raji cell line and fibrosarcoma tumor bearing Swiss mice, respectively.

Results: 68Ga-acridine complex was obtained with ~100% radiochemical purity under the optimized reaction conditions involving incubation of 2mg/mL of ligand at 100°C for 30 minutes. The complex maintained a radiochemical purity of >95% in normal saline and >65% in human blood serum at 3h post-incubation. In vitro cellular study showed (3.2±0.1)% uptake of the radiotracer in the Raji cells. Biodistribution study revealed significant tumor accumulation [(11.41±0.41)% injected activity in per gram] of the radiotracer within 1h postadministration along with uptake in other non-target organs such as, blood, liver, GIT kidney etc.

Conclusion: The present study indicates the potential of 68Ga-acridine as a PET agent for imaging of tumorous lesions. However, further detailed evaluation of the agent is warranted to explore its actual potential.

Keywords: Radiolabeled DNA intercalator, 68Ga-acridine, PET radiotracer, tumor imaging, fibrosarcoma, acridine-DOTA conjugate.

Graphical Abstract

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