Abstract
PurposeMany 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 [18F]DPA-714 for positron emission tomography (PET) imaging of cancer and inflammation.Procedures[18F]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[18F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceable [18F]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 [18F]DPA-714 metabolism and muscle clearance in mice compared to rats may explain the elevated background signal in peripheral organs in this species.ConclusionAlthough TSPO is an evolutionary conserved protein, inter- and intra-species differences call for further exploration of the pharmacological parameters of TSPO radioligands.Electronic supplementary materialThe online version of this article (doi:10.1007/s11307-015-0877-x) contains supplementary material, which is available to authorized users.
Highlights
The 18-kDa translocator protein (TSPO) is a member of the evolutionary conserved transporter protein family [1]
TSPO has generated much interest as an imaging target, and a large number of TSPO radioligands have been synthesized for positron emission tomography (PET) imaging including [11C]PK11195, [11C]DAA1106, [11C]PBR28, [18F]PBR06, [11C]SSR180575, and [18F]DPA-714 [3, 17, 18]
Pharmacokinetics analysis was performed by fitting a bi-exponential model to the blood time-activity curves (TACs) for each animal and calculating the distribution half-life (t1/2α) and elimination half-life (t1/2β) of [18F]DPA714. [18F]DPA-714 uptake was expressed as %ID/g, lesion-to-muscle ratios of %ID/g, as well as using the standardized uptake value (SUV) calculated as/[(injected activity)/ (g of body weight)]
Summary
The 18-kDa translocator protein (TSPO) is a member of the evolutionary conserved transporter protein family [1]. Successful preclinical imaging evaluations have triggered the clinical use of several TSPO radioligands in small cohorts of patients [19] The majority of these preclinical studies investigated TSPO PET radiotracers in models of neuroinflammation (e.g., Alzheimer’s disease [20], stroke [21], multiple sclerosis [22], and glioma [23, 24]), generally in the rat due to the small size of the mouse brain. For the peripheral inflammation model, 1 μl turpentine oil was injected intramuscularly into the right inner thigh of female nude NMRI mice and 10 μl into Wistar rats. Imaging of these acute inflammatory lesions was conducted 24 h postinduction. The inflammatory bowel disease model of colitis in C57BL/6 mice and Wistar rats was established by introducing 2.5 % of dextran sulfate sodium (DSS) daily in the animals’ drinking water for 7–8 days
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