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j.nucmedbio.2014.10.006.pdf | 683.79 kB | Adobe PDF | 見る/開く |
タイトル: | Radiofluorinated probe for PET imaging of fatty acid binding protein 4 in cancer. |
著者: | Temma, Takashi Nishigori, Kantaro Onoe, Satoru Sampei, Sotaro Kimura, Ikuo https://orcid.org/0000-0001-8778-145X (unconfirmed) Ono, Masahiro https://orcid.org/0000-0002-2497-039X (unconfirmed) Saji, Hideo |
著者名の別形: | 天滿, 敬 佐治, 英郎 |
キーワード: | Fatty acid binding protein 4 Radiolabeled probe Positron emission tomography PET Nuclear imaging |
発行日: | Feb-2015 |
出版者: | Elsevier Inc. |
誌名: | Nuclear medicine and biology |
巻: | 42 |
号: | 2 |
開始ページ: | 184 |
終了ページ: | 191 |
抄録: | 【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. |
著作権等: | © 2014 Elsevier Inc. 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。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/193665 |
DOI(出版社版): | 10.1016/j.nucmedbio.2014.10.006 |
PubMed ID: | 25457456 |
出現コレクション: | 学術雑誌掲載論文等 |
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