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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Research Article

The Influence of Kidneys Ion Transport Inhibitors on the Pharmacokinetic and Tumor Uptake Behaviors of a HER2-targeted Small Size Radiolabeled Peptide

Author(s): Nasrin Abbasi Gharibkandi, Sajjad Molavipordanjani, Alireza Mardanshahi and Seyed Jalal Hosseinimehr*

Volume 23, Issue 1, 2022

Published on: 14 February, 2022

Page: [82 - 87] Pages: 6

DOI: 10.2174/1389200223666220113101004

Price: $65

Abstract

Background: HER2 over-expression plays a crucial role in the cancer treatment protocol. This study evaluates the effectiveness of organic anion and cation transport inhibitors and substrate on the tumor uptake of 99mTc- HYNIC-(Ser)3-LTVPWY radiotracer in SKOV-3 tumor-bearing nude mice.

Methods: Before the injection of the radiolabeled peptide, SKOV-3 tumor-bearing nude mice were treated with furosemide, cimetidine, para-amino hippuric acid, and saline. The inhibition effects of the organic anion and cation transport inhibitors were compared with the control group. In both treatment and control groups, the tumor and renal accumulation of radiopeptide in mice bearing SKOV-3 tumors were assessed in biodistribution and SPECT imaging studies.

Results: The biodistribution and imaging results suggested that all treated groups showed a higher tumor and higher normal tissue radioactivity compared to the control group. According to the tumor imaging study, the furosemidetreated group had slightly better tumor uptake and a higher tumor to muscle uptake ratio than other treatment groups.

Conclusion: Administration of furosemide (an OAT inhibitor) increased radioactivity accumulation in the kidneys and blood and improved tumor radioactivity uptake. PAH (an anion transporter substrate) and cimetidine (an OCT inhibitor) have a minor effect on the accumulation of radioactivity in the kidneys and the acquired images.

Keywords: Kidney transport inhibitors, 99mTc-HYNIC-(Ser)3-LTVPWY, radiolabeled peptide, HER2, tumor imaging, tumor targeting, cation transport inhibitors, anion transport inhibitors.

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