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Title: Radiofluorinated probe for PET imaging of fatty acid binding protein 4 in cancer.
Authors: Temma, Takashi
Nishigori, Kantaro
Onoe, Satoru
Sampei, Sotaro
Kimura, Ikuo
Ono, Masahiro  kyouindb  KAKEN_id
Saji, Hideo
Author's alias: 天滿, 敬
佐治, 英郎
Keywords: Fatty acid binding protein 4
Radiolabeled probe
Positron emission tomography
PET
Nuclear imaging
Issue Date: Feb-2015
Publisher: Elsevier Inc.
Journal title: Nuclear medicine and biology
Volume: 42
Issue: 2
Start page: 184
End page: 191
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.
Rights: © 2014 Elsevier Inc.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/193665
DOI(Published Version): 10.1016/j.nucmedbio.2014.10.006
PubMed ID: 25457456
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