Abstract LB-144: In vivo detection of bone metastases in a mouse model by positron emission tomography (PET) with [F-18]-labeled tyrosine derivative (D-FMT)

Abstract

Abstract Objective: Detection and localization of metastatic lesions in advanced stages of cancer is still a difficult obstacle for diagnosis and subsequent treatment decisions for an optimized cancer patient management and therapy control. Whole body molecular imaging applying positron emission tomography (PET) allows the sensitive detection of radioactive labeled molecules, which specifically accumulate in tumor tissue. This offers a promising tool to assess the stage of the disease comprehensively. At present [F-18]-fluorodeoxyglucose (FDG) is the mostly used PET-tracer in oncology. However, FDG has the disadvantageof limited specificity by accumulating also in inflammatory cells due to their increased glucose metabolism. To overcome this problem, amino acids have been radiolabeled to study their potential imaging characteristics. D-[F-18]-fluoromethyl tyrosine (D-FMT, (R)-2-amino-3-(4-[F-18]fluoromethoxy-phenyl)-propionic acid) has shown good uptake into HeLa tumors in nude mice with no accumulation in sterile induced inflammation sites. The aim of this study was to investigate if D-FMT can also be used to image bone metastases besides primary soft tissue tumors. Methods: Human 786-O/luciferase renal cell adenocarcinoma cells were injected intracardially, which gave rise to the formation of several bone metastases. The radiosynthesis of D-FMT was carried out using an indirect labeling method via the [F-18]-fluoromethyl bromide synthon. Micro-PET imaging was performed 51 and 65 days after tumor cell inoculation. Results: The formation of metastases was monitored using bioluminescence imaging indicating the presence of tumor cells in the regions of hind limbs, forelimbs, spine and skull. A bone scan with [F-18]-fluoride confirmed skeletal metabolic activity at sites of osteolytic bone metastases. The i.v. application of [F-18]-D-FMT showed a very specific accumulation of the amino acid tracer in these bone metastases and, together with the low background, allowed very good imaging of these lesions. Based on the PET scan of [F-18]-D-FMT, sites of accumulation were excised. All imaged metastases could be verified histologically. Conclusion: These data suggest D-FMT as a new potential imaging tracer for the detection of primary tumors as well as bone metastases. In addition, the sensitivity of this tracer suggests the possibility for substantial benefit in detecting soft tissue metastases as well. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-144.