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

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.

• Authors: Jinzi Zheng, Alexandra Winkeler, Marie-Anne Peyronneau, Frédéric Dollé, Raphaël Boisgard
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 18 Issue 1 Pg. 127-34 (Feb 2016) ISSN: 1860-2002 [Electronic] United States
• PMID: 26194010 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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