Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.
Radiological Center, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji, Fukui 910-1193, Japan.
Int J Mol Sci. 2024 Jul 15;25(14):7747. doi: 10.3390/ijms25147747.
[I]β-methyl-p-iodophenyl-pentadecanoic acid ([I]BMIPP), which is used for nuclear medicine imaging of myocardial fatty acid metabolism, accumulates in cancer cells. However, the mechanism of accumulation remains unknown. Therefore, this study aimed to elucidate the accumulation and accumulation mechanism of [I]BMIPP in cancer cells. We compared the accumulation of [I]BMIPP in cancer cells with that of [F]FDG and found that [I]BMIPP was a much higher accumulation than [F]FDG. The accumulation of [I]BMIPP was evaluated in the presence of sulfosuccinimidyl oleate (SSO), a CD36 inhibitor, and lipofermata, a fatty acid transport protein (FATP) inhibitor, under low-temperature conditions and in the presence of etomoxir, a carnitine palmitoyl transferase I (CPT1) inhibitor. The results showed that [I]BMIPP accumulation was decreased in the presence of SSO and lipofermata in H441, LS180, and DLD-1 cells, suggesting that FATPs and CD36 are involved in [I]BMIPP uptake in cancer cells. [I]BMIPP accumulation in all cancer cell lines was significantly decreased at 4 °C compared to that at 37 °C and increased in the presence of etomoxir in all cancer cell lines, suggesting that the accumulation of [I]BMIPP in cancer cells is metabolically dependent. In a biological distribution study conducted using tumor-bearing mice transplanted with LS180 cells, [I]BMIPP highly accumulated in not only LS180 cells but also normal tissues and organs (including blood and muscle). The tumor-to-intestine or large intestine ratios of [I]BMIPP were similar to those of [F]FDG, and the tumor-to-large-intestine ratios exceeded 1.0 during 30 min after [I]BMIPP administration in the in vivo study. [I]BMIPP is taken up by cancer cells via CD36 and FATP and incorporated into mitochondria via CPT1. Therefore, [I]BMIPP may be useful for imaging cancers with activated fatty acid metabolism, such as colon cancer. However, the development of novel imaging radiotracers based on the chemical structure analog of [I]BMIPP is needed.
β-甲基-p-碘代苯戊十五烷酸（[I]BMIPP）可用于核医学成像心肌脂肪酸代谢，会在癌细胞中积聚。然而，其积聚的机制尚不清楚。因此，本研究旨在阐明[I]BMIPP 在癌细胞中的积聚及其积聚机制。我们比较了[I]BMIPP 在癌细胞中的积聚与[F]FDG 的积聚，发现[I]BMIPP 的积聚明显高于[F]FDG。在低温条件下，使用 CD36 抑制剂磺基琥珀酰亚胺辛酯（SSO）和脂肪酸转运蛋白（FATP）抑制剂 lipofermata，以及肉碱棕榈酰转移酶 I（CPT1）抑制剂 etomoxir 评价[I]BMIPP 的积聚。结果表明，在 H441、LS180 和 DLD-1 细胞中，SSO 和 lipofermata 的存在降低了[I]BMIPP 的积聚，表明 FATPs 和 CD36 参与了癌细胞摄取[I]BMIPP。与 37°C 相比，所有癌细胞系在 4°C 时[I]BMIPP 的积聚显著减少，并且在所有癌细胞系中加入 etomoxir 后[I]BMIPP 的积聚增加，提示[I]BMIPP 在癌细胞中的积聚是代谢依赖性的。在使用 LS180 细胞移植瘤的荷瘤小鼠的生物分布研究中，[I]BMIPP 不仅在 LS180 细胞中高度积聚，而且在正常组织和器官（包括血液和肌肉）中也高度积聚。在体内研究中，[I]BMIPP 的肿瘤-肠道或大肠比值与[F]FDG 相似，在[I]BMIPP 给药后 30 分钟内，肿瘤-大肠比值超过 1.0。[I]BMIPP 通过 CD36 和 FATP 被癌细胞摄取，并通过 CPT1 掺入线粒体。因此，[I]BMIPP 可能对成像脂肪酸代谢活跃的癌症（如结肠癌）有用。然而，需要开发基于[I]BMIPP 化学结构类似物的新型成像放射性示踪剂。
