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Assessment of P-Glycoprotein in Patients with Malignant Bone and Soft-Tissue Tumors Using Technetium-99m-MIBI Scintigraphy

Departments of Nuclear Medicine and Orthopedics, Kanazawa University School of Medicine, Kanzawa; Department of Pathology, Kanazawa Medical University, Uchinada, Japan

Correspondence: For correspondence or reprints contact: Junichi Taki, MD, Department of Nuclear Medicine, Kanazawa University School of Medicine, 13–1 Takara-machi, Kanazawa, 9208640 Japan.

ABSTRACT

Overexpression of P-glycoprotein (Pgp) has been detected in many malignant tumors including bone and soft-tissue tumors. Technetium-99m-MIBI has proved to be a transport substrate for Pgp. The purpose of our study was to explore ^99mTc-MlBI as a functional imaging agent reflecting Pgp expression in malignant bone and soft-tissue tumors. Methods: Technetium-99m-MIBI scintigraphy was performed in 30 patients with malignant bone and soft-tissue tumors. Radionuclide angiography with ^99mTc-MIBI was done and, at 15 min and 3 hr postinjection ofthe radiopharmaceutical, imaging was performed. The ^99mTc-MIBI uptake ratio was calculated by dividing the lesion count by the background count. The washout rate (WR)for ^99mTc-MIBI was calculated by the following formula: WR = 100 x [(Te-Be)-(Td-Bd)]/(Te-Be)(%), where Te and Td = decay corrected count density of the tumor in the 15-min and 3-hr images, respectively. Be and Bd = decay-corrected count density of the background in the 15-min and 3-hr images, respectively. The lesions were resected by open biopsy to obtain a histopathological diagnosis, and immunohistochemical staining was performed to detect Pgp. Results: Twenty-four of 30 patients showed significant uptake at the 15-min image. In these 24 patients, the lesions with a high Pgp expression showed a similar ^99mTc-MIBl perfusion index (3.00 ± 1.04)and uptake ratio (2.05 ± 0.58) at the 15-mmimageto thoseof lesions without a high Pgp expression (2.65 ± 0.85 and 2.28 ± 0.64, respectively). On delayed images,the ^99mTc-MIBI uptake ratio was lower in patients with a high Pgp expression than in patients without a high Pgp expression (1.37 ± 0.41 versus 1.87 ± 0.39, p < 0.01). The washout ratio of ^99mTc-MlBI was higher in patients with a high Pgp expression than in patients without a high Pgp expression (66% ± 25% versus 29% ± 18%, p < 0.001). None of the 6 patients without ^99mTc-MIBI uptake at the 15-min imaging showed ²⁰¹TI uptake, and only 2 had a high Pgp expression. Conclusion: In malignant bone and soft-tissue tumors, perfusion and initial ^99mTc-MIBI uptake were not related to the Pgp expression; however, washout of ^99mTc-MlBI from the tumor was related to Pgp expression. Technetium-99m-MIBI scintigraphy with washout analysis may be a useful method for the evaluation of Pgp overexpression and its function.

Key Words: technetium-99m-MIBI • P-glycoprotein • multidrug resistance • bone tumor • soft-tissue tumor

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