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^99mTc-MIBI/²⁰¹Tlシンチグラフィによるマウス腫瘍のタキソール抵抗性の評価：織内 昇¹, 治部達夫², 遠藤啓吾¹（¹群馬大・医・核, ²帝京大・医・外）

Assessment of resistance to paclitaxel of murine tumors by ^99mTc-MIBI/²⁰¹Tl scintigraphy: Noboru ORIUCHI¹, Tatsuo JIBU², Keigo ENDO¹（¹Dept. of Nucl. Med., Gunma Univ., ²Dept. of Surg., Teikyo Univ.）

This study investigates P-glycoprotein (Pgp) expression by murine tumors with and without resistance to paclitaxel and the role of Tc-99m-hexakis 2-methoxyisobutyl-isonitrile (^99mTc-MIBI)/[²⁰¹Tl]thallous chloride (²⁰¹Tl) dual-radionuclide imaging in predicting the effect of paclitaxel therapy. Mice were implanted with one of the following four murine tumors: mammary carcinoma (M), ovarian carcinoma (O), hepatic cell carcinoma (H), or fibrosarcoma (F). The antitumor effect of paclitaxel was evaluated by measuring tumor growth after i.v. injection of paclitaxel (40 mg/kg). The biodistribution of ^99mTc-MIBI and ²⁰¹Tl was evaluated at 10, 30, and 120 min after i.v. injection of the two radiopharmaceuticals. Sequential imaging with these agents was also performed. Expression of Pgp was examined with immunohistochemical staining and western blotting of the tumors. M and O responded to paclitaxel and showed delayed tumor growth, but H and F did not respond to it. Increased expression of Pgp was noted in M and O and these two tumors showed higher uptake of ^99mTc-MIBI at 10 and 30 min after injection than the other two (P < 0.001). F showed significantly fast washout of ^99mTc-MIBI from the tumor. ²⁰¹Tl uptake was independent of response to paclitaxel or Pgp expression. Pgp expression did not correlate with the antitumor efficacy of paclitaxel and is unlikely to be the major mechanism responsible for tumor resistance to paclitaxel. Although the absolute uptake of ^99mTc-MIBI did not correlate with Pgp expression, it was predictive of paclitaxel sensitivity. ²⁰¹Tl uptake improved the ability of ^99mTc-MIBI imaging to distinguish paclitaxel-sensitive from paclitaxel-resistant tumors.