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NIH Research Festival

September 13 – 15, 2017

Application of positron emission tomography (PET) for the study of the pharmacokinetics of albumin-binding radioligands in mice

Friday, September 15, 2017 – Poster Session IV
1:00 – 2:30 p.m.

FAES Terrace

NIBIB

PHARM-3

Authors

  • DO Kiesewetter
  • O Jacobson
  • R Tian
  • Z Wang
  • G Niu
  • X Chen

Abstract

Introduction: We have developed radioligands for targeted imaging of tumor markers and evaluated the pharmacokinetics of these ligands using positron emission tomography (PET). PET is a very sensitive imaging method that can achieve a resolution of 1.0 – 1.5 mm for small animal imaging. The ligands were modified to provide more favorable pharmacokinetics, which can be measured by exploiting PET. Methods: We prepared and radiolabeled analogs of clinically relevant tumor imaging agents for somatostatin, integrin, and prostate specific membrane antigen conjugated with an albumin binding moiety based on Evans blue. These analogs were expected to exhibit much slower clearance from the blood and to result in agents that can be used for diagnostic imaging or radiotherapy when used with appropriate radionuclides. The blood half-life and tumor uptake were evaluated using PET/CT imaging. Results: The blood half-life of the conjugates with an albumin binding domain were enhanced by a factor of at least 2, compared to the parent ligand. The blood retention was much higher resulting in significantly increased tumor uptake and area under the curve. Tumor uptakes ranged from 30 - 70 %ID/g at 24 h depending on the modified ligand and tumor model. In addition, the contrast of the image compared to background muscle tissue was greater than 20 at 24 h post-injection. Conclusions: Conjugation of albumin binding moieties resulted in more favorable pharmacokinetics that allowed increased PET image contrast. The much higher tumor uptake suggests that lower doses of radionuclide will be required for effective therapy.

Scientific Focus Area: Molecular Pharmacology

This page was last updated on Friday, March 26, 2021

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