Evaluation of PET Imaging Performance of the TSPO Radioligand [18F]DPA-714 in Mouse and Rat Models of Cancer and Inflammation

Mol Imaging Biol. 2016 Feb;18(1):127-34. doi: 10.1007/s11307-015-0877-x.

Abstract

Purpose: Many radioligands have been explored for imaging the 18-kDa translocator protein (TSPO), a diagnostic and therapeutic target for inflammation and cancer. Here, we investigated the TSPO radioligand [(18)F]DPA-714 for positron emission tomography (PET) imaging of cancer and inflammation.

Procedures: [(18)F]DPA-714 PET imaging was performed in 8 mouse and rat models of breast and brain cancer and 4 mouse and rat models of muscular and bowel inflammation.

Results: [(18)F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceable [(18)F]DPA-714 binding is observed ex vivo, TSPO-positive PET imaging of peripheral lesions of cancer and inflammation in mice did not show significant lesion-to-background signal ratios. Slower [(18)F]DPA-714 metabolism and muscle clearance in mice compared to rats may explain the elevated background signal in peripheral organs in this species.

Conclusion: Although TSPO is an evolutionary conserved protein, inter- and intra-species differences call for further exploration of the pharmacological parameters of TSPO radioligands.

Keywords: Cancer; DPA-714; Inflammation; PET imaging; TSPO.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Humans
  • Inflammation / complications
  • Inflammation / diagnostic imaging*
  • Inflammation / pathology
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasms / complications
  • Neoplasms / diagnostic imaging*
  • Neoplasms / pathology
  • Positron-Emission Tomography / methods*
  • Pyrazoles / blood
  • Pyrazoles / metabolism*
  • Pyrazoles / pharmacokinetics
  • Pyrimidines / blood
  • Pyrimidines / metabolism*
  • Pyrimidines / pharmacokinetics
  • Radiopharmaceuticals / metabolism*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats, Wistar
  • Receptors, GABA / metabolism*
  • Receptors, GABA-A / metabolism*
  • Tissue Distribution

Substances

  • Bzrp protein, mouse
  • Carrier Proteins
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • Pyrazoles
  • Pyrimidines
  • Radiopharmaceuticals
  • Receptors, GABA
  • Receptors, GABA-A
  • Tspo protein, rat