四苯基鏻作为一种新型肿瘤成像分子探针。

Tetraphenylphosphonium as a novel molecular probe for imaging tumors.

作者信息

Min Jung-Jun, Biswal Sandip, Deroose Christophe, Gambhir Sanjiv S

机构信息

Department of Radiology and the Bio-X Program, Stanford University School of Medicine, Stanford, California, USA.

出版信息

J Nucl Med. 2004 Apr;45(4):636-43.

PMID:15073261

Abstract

UNLABELLED

Mitochondrial membrane potential (DeltaPsim)-dependent enhanced uptake of phosphonium salts, including (3)H-tetraphenylphosphonium ((3)H-TPP), in tumor cells, suggests the potential use of phosphonium salts as tracers for tumor imaging. In this study, we characterize the tumor accumulation of (3)H-TPP and compare it with (18)F-FDG in cell culture and in xenograft, metastatic, and inflammation models in living animals.

METHODS

(3)H-TPP and (3)H-FDG accumulation was compared in cell culture with a variety of cell lines in different glucose concentrations. Normal biodistribution and tumor uptake were assessed using nude mice with or without subcutaneous xenograft tumors (C6). To compare the accumulation of (3)H-TPP and (18)F-FDG in a metastatic tumor, severe combined immunodeficiency mice were tail-vein injected with human melanoma cell lines (A375-FL). To characterize the accumulation of (3)H-TPP and (18)F-FDG in inflammation, an inflammatory reaction was induced by subcutaneous injection of Complete Freund's Adjuvant in the left hind paw of Sprague-Dawley rat.

RESULTS

The DeltaPsim data from a separate study and the current (3)H-TPP uptake data showed good correlation (r(2) = 0.82, P < 0.05). (3)H-TPP accumulation was significantly greater than that of (3)H-FDG for glucose >/=100 mg/dL. The biodistribution study of (3)H-TPP showed low uptake in most tissues but high accumulation in the heart and kidneys. (3)H-TPP accumulation in xenograft or metastatic tumors was comparable with that of (18)F-FDG, whereas (3)H-TPP accumulation in inflammatory tissues was markedly lower than that of (18)F-FDG.

CONCLUSION

The sensitive tumor accumulation of (3)H-TPP with less propensity for inflammatory regions warrants further investigation of radiolabeled phosphonium analogs for tumor imaging in living subjects.

摘要

未标记

肿瘤细胞中线粒体膜电位（ΔΨm）依赖性增强的鏻盐摄取，包括（3）H - 四苯基鏻（（3）H - TPP），提示鏻盐作为肿瘤成像示踪剂的潜在用途。在本研究中，我们在细胞培养以及活体动物的异种移植、转移和炎症模型中，对（3）H - TPP的肿瘤蓄积进行了表征，并将其与（18）F - FDG进行比较。

方法

在不同葡萄糖浓度下，比较（3）H - TPP和（3）H - FDG在多种细胞系中的细胞培养蓄积情况。使用有或没有皮下异种移植肿瘤（C6）的裸鼠评估正常生物分布和肿瘤摄取。为比较（3）H - TPP和（18）F - FDG在转移瘤中的蓄积，给严重联合免疫缺陷小鼠尾静脉注射人黑色素瘤细胞系（A375 - FL）。为表征（3）H - TPP和（18）F - FDG在炎症中的蓄积，通过在Sprague - Dawley大鼠左后爪皮下注射完全弗氏佐剂诱导炎症反应。

结果

来自另一项研究的ΔΨm数据与当前的（3）H - TPP摄取数据显示出良好的相关性（r² = 0.82，P < 0.05）。当葡萄糖≥100mg/dL时，（3）H - TPP的蓄积显著大于（3）H - FDG。（3）H - TPP的生物分布研究显示在大多数组织中摄取较低，但在心脏和肾脏中蓄积较高。（3）H - TPP在异种移植瘤或转移瘤中的蓄积与（18）F - FDG相当，而（3）H - TPP在炎症组织中的蓄积明显低于（18）F - FDG。