Radiofluorinated probe for PET imaging of fatty acid binding protein 4 in cancer
| Autor: | Hideo Saji, Satoru Onoe, Kantaro Nishigori, Masahiro Ono, Sotaro Sampei, Ikuo Kimura, Takashi Temma |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cancer Research Biodistribution Positron emission tomography Fluorine Radioisotopes Radiolabeled probe Cell Naphthalenes Fatty Acid-Binding Proteins Fatty acid-binding protein Permeability Mice In vivo 3T3-L1 Cells Cell Line Tumor medicine Animals Radiology Nuclear Medicine and imaging Tissue Distribution Fatty acid binding protein 4 Radiochemistry Chemistry Radiosynthesis Glioma Triazoles In vitro Rats medicine.anatomical_structure PET Biochemistry Drug Design Positron-Emission Tomography Cancer cell Biophysics Molecular Medicine Nuclear imaging Ex vivo |
| Zdroj: | Nuclear medicine and biology. 42(2) |
| ISSN: | 1872-9614 |
| Popis: | Introduction Cancer-associated adipocytes metabolically interact with adjacent cancer cells to promote tumor proliferation and metastasis. Fatty acid binding protein 4 (FABP4) participates in this interaction, and is gathering attention as a therapeutic and diagnostic target. Positron emission tomography (PET) is a useful diagnostic method that enables noninvasive in vivo quantitative imaging of biofunctional molecules with probes labeled with positron-emitting radioisotopes. Here a novel 18 F labeled probe for PET FABP4 imaging developed through dedicated drug design from a radioiodinated probe we recently reported is evaluated in vitro and in viv o. Methods We designed the [ 18 F]-labeled FTAP1 and FTAP3 probe, composed of a single or triple oxyethylene linker and a triazolopyrimidine scaffold derived from an FABP4 inhibitor. FABP4 binding affinities for chemically synthesized FTAP1 and FTAP3 were measured using FABP4 and 8-anilino-1-naphthalene sulfonic acid. Cell membrane permeability was measured using a commercially available plate assay system. After radiosynthesis, [ 18 F]FTAP1 affinity and selectivity were evaluated using immobilized FABP3, FABP4, and FABP5. Cell uptake was investigated using differentiated adipocytes expressing FABP4 with inhibitor treatment. Following biodistribution studies in C6 glioblastoma-bearing mice, ex vivo autoradiography and immunohistochemistry were performed using thin sliced tumor sections. PET/CT imaging was then performed on C6 tumor bearing mice. Results FTAP1 showed high FABP4 affinity ( K i =68±8.9 nM) and adequate cell permeability. [ 18 F]FTAP1 with ≥98% radiochemical purity was shown to selectively bind to FABP4 (16.3- and 9.3-fold higher than for FABP3 and FABP5, respectively). [ 18 F]FTAP1 was taken up by FABP4 expressing cells, and this uptake could be blocked by an inhibitor, indicating very low non-specific cell binding. [ 18 F]FTAP1 showed high tumor accumulation, which demonstrates its potential use for in vivo tumor PET imaging, and the intratumoral radioactivity distribution corresponded to the FABP4 expression profile. Conclusion [ 18 F]FTAP1 is a promising PET probe to target FABP4. |
| Databáze: | OpenAIRE |
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