Design of 99mTc-labeled zinc-chelating imaging probe for SPECT imaging of the pancreas

Venkateswararao Eeda; Andria Hedrick; Vibhudutta Awasthi

doi:10.1016/j.bmcl.2021.128385

Design of ^99mTc-labeled zinc-chelating imaging probe for SPECT imaging of the pancreas

Bioorg Med Chem Lett. 2021 Nov 15:52:128385. doi: 10.1016/j.bmcl.2021.128385. Epub 2021 Sep 27.

Authors

Venkateswararao Eeda¹, Andria Hedrick¹, Vibhudutta Awasthi²

Affiliations

¹ Department of Pharmaceutical Sciences, College of Pharmacy, 1110 North Stonewall Avenue, University of Oklahoma Health Sciences Center, and Oklahoma City, Oklahoma 73117, USA.
² Department of Pharmaceutical Sciences, College of Pharmacy, 1110 North Stonewall Avenue, University of Oklahoma Health Sciences Center, and Oklahoma City, Oklahoma 73117, USA. Electronic address: vawasthi@ouhsc.edu.

PMID: 34592436
DOI: 10.1016/j.bmcl.2021.128385

Abstract

Early and sensitive diagnosis of pancreatic diseases is a contemporary clinical challenge. Zinc level in pancreatic tissue and its secretion in pancreatic juice has long been considered a surrogate marker of pancreatic function. The objective of this study was to design a Zn-chelating imaging probe (ZCIP) which could be labeled with ^99mTc radionuclide for imaging of pancreas using single photon emission tomography (SPECT). We synthesized ZCIP as a bifunctional chelate consisting of diethylene triamine pentaacetic acid for ^99mTc-chelation at one end and bispicolylethylamine for Zn-complexation at the other end. ZCIP was labeled with ^99mTc by standard Sn²⁺-based reduction method. The ^99mTc-labeled ZCIP was studied in normal mice (0.3 mCi) for SPECT imaging. We found that ZCIP consistently labeled with ^99mTc radionuclide with over 95% efficiency. Addition of ZCIP altered the spectrum of standard dithizone-Zn complex, indicating its ability to chelate Zn. SPECT data demonstrated the ability of ^99mTc-ZCIP to image pancreas with high sensitivity in a non-invasive manner; liver and spleen were the other major organs of ^99mTc-ZCIP uptake. Based on these results, we conclude that ^99mTc-ZCIP presents as a novel radiotracer for pancreas imaging for diagnosis of diseases such as pancreatitis.

Keywords: Chronic pancreatitis; Pancreas imaging; Pancreatic cancer; SPECT; Zinc.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chelating Agents / chemical synthesis
Chelating Agents / chemistry*
Drug Design
Mice
Molecular Probes / chemical synthesis
Molecular Probes / chemistry*
Molecular Structure
Pancreas / diagnostic imaging*
Technetium / chemistry*
Tomography, Emission-Computed, Single-Photon*
Zinc / chemistry*

Substances

Chelating Agents
Molecular Probes
Technetium
Zinc