Radiofluorinated probe for PET imaging of fatty acid binding protein 4 in cancer.

• Temma, Takashi

• Nishigori, Kantaro

• Onoe, Satoru

• Sampei, Sotaro

• Kimura, Ikuo

• Ono, Masahiro

• Saji, Hideo

Abstract

【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 18F labeled probe for PET FABP4 imaging developed through dedicated drug design from a radioiodinated probe we recently reported is evaluated in vitro and in vivo.【Methods】We designed the [18F]-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, [18F]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 (Ki = 68 ± 8.9 nM) and adequate cell permeability. [18F]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). [18F]FTAP1 was taken up by FABP4 expressing cells, and this uptake could be blocked by an inhibitor, indicating very low non-specific cell binding. [18F]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】][18F]FTAP1 is a promising PET probe to target FABP4.

Journal

• Nuclear medicine and biology

  Nuclear medicine and biology 42 (2), 184-191, 2015-02

  Elsevier Inc.

Keywords

• Fatty acid binding protein 4
• Radiolabeled probe
• Positron emission tomography
• PET
• Nuclear imaging

Details

• CRID: 1050564285755958400
• NII Article ID: 120005539357
• NII Book ID: AA10864894
• ISSN: 09698051
• HANDLE: 2433/193665
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles