Translocator Protein PET Imaging in a Preclinical Prostate Cancer Model

Abstract

Purpose The identification and targeting of biomarkers specific to prostate cancer (PCa) could improve its detection. Given the high expression of translocator protein (TSPO) in PCa, we investigated the use of [18F]VUIIS1008 (a novel TSPO-targeting radioligand) coupled with positron emission tomography (PET) to identify PCa in mice and to characterize their TSPO uptake. Procedures Ptenpc−/−, Trp53pc−/− prostate cancer-bearing mice (n = 9, 4–6 months old) were imaged in a 7T MRI scanner for lesion localization. Within 24 h, the mice were imaged using a microPET scanner for 60 min in dynamic mode following a retro-orbital injection of ~ 18 MBq [18F]VUIIS1008. Following imaging, tumors were harvested and stained with a TSPO antibody. Regions of interest (ROIs) were drawn around the tumor and muscle (hind limb) in the PET images. Time-activity curves (TACs) were recorded over the duration of the scan for each ROI. The mean activity concentrations between 40 and 60 min post radiotracer administration between tumor and muscle were compared. Results Tumor presence was confirmed by visual inspection of the MR images. The uptake of [18F]VUIIS1008 in the tumors was significantly higher (p < 0.05) than that in the muscle, where the percent injected dose per unit volume for tumor was 7.1 ± 1.6 % ID/ml and that of muscle was < 1 % ID/ml. In addition, positive TSPO expression was observed in tumor tissue analysis. Conclusions The foregoing preliminary data suggest that TSPO may be a useful biomarker of PCa. Therefore, using TSPO-targeting PET ligands, such as [18F]VUIIS1008, may improve PCa detectability and characterization.

Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

“…A cell-type specific transcription pattern of Tspo mRNA was observed. Consistent with previous studies [ 41 ], which demonstrated the presence of TSPO protein in the prostate [ 23 , 26 , 42 , 43 , 44 ], brain [ 38 , 44 , 45 , 46 , 47 , 48 ], stomach [ 23 , 44 ], colon [ 23 , 29 , 44 , 49 ], liver [ 23 , 44 , 50 , 51 , 52 ], lung [ 23 , 44 , 53 ], breast [ 23 , 54 ], and kidney [ 21 , 55 , 56 ]. Tspo mRNA transcription was observed to occur in most epithelial cells of the prostate, glia, and neurons of the brain, parietal cells, chief cells, and in the surface and neck mucous cells of the gastric glands of the stomach, hepatocytes, endothelial cells of the sinusoids, and Kupffer cells of the liver, most of the epithelial cells, goblet cells, and absorptive cells of the colon, most of the epithelial cells and macrophages of the lung, most of the epithelial cells of breast, most of the epithelial cells of the PCT, vasa recta, thin ascending and descending limbs, thick ascending limb, DCT, collecting tubule, collecting duct, and in the endothelial cells of the glomerulus of the kidney.…”

“…Consistent with previous studies a relative increase in Tspo mRNA transcription was observed in Grades II and III prostate adenocarcinoma of the peripheral duct and acini [26,42,65] and Grade II brain diffuse fibrillary astrocytoma [24]. In our study, only fluorescent detection of immunohistochemistry (IHC) staining indicated a significant increase in Tspo transcription in liver cancer, prostate cancer, and brain cancer.…”

Evaluation of [18F]F-DPA as a target for TSPO in head and neck cancer under normal conditions and after radiotherapy

“…Imaging of TSPO in cancer could therefore be a useful tool in treatment planning and/or for the development of new TSPO-targeting drugs. Apart from brain gliomas, only a few preclinical studies have evaluated TSPO-PET tracers in peripherally located tumours [5][6][7][8][9]. Many of these reports focused on evaluating the relationship between tracer uptake and tumour inflammation and/ or levels of macrophages [5][6][7][8].…”

“…Several studies [5,6,8] have reported that TSPO imaging has potential in measuring macrophage levels in tumours, whereas Zheng et al [7] reported on a low lesion-to-background uptake with [ 18 F]DPA-714 in several models for cancer and inflammation. Tantawy et al [9] concluded that [ 18 F]VUIIS1008 might be a useful tracer for TSPO-targeting in prostate cancer.…”

The Place of PET to Assess New Therapeutic Effectiveness in Neurodegenerative Diseases

“…More recently, TSPO PET imaging has been shown to assume a promising involvement in the development of diagnostic strategies in cancer. More recently, TSPO has been introduced as a possible molecular target for peripheral sterile inflammatory diseases PET imaging, making this protein a potential biomarker with the aim of addressing disease heterogeneity, assisting in patient stratification, and contributing to predicting treatment response [ 86 – 88 ]. Finally, amyloid tracers such as 18 F-florbetapir or 11 C-PIB may be promising PET radiotracers for imaging amyloid deposit in cardiac amyloidosis [ 89 , 90 ], considering that they also exhibit specific affinity for myocardial amyloid fibers.…”