Assessment of P-glycoprotein in patients with malignant bone and soft-tissue tumors using technetium-99m-MIBI scintigraphy

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-MIBI 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 of the 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-MIBI perfusion index (3.00 +/- 1.04) and uptake ratio (2.05 +/- 0.58) at the 15-min image to those of 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-MIBI 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-MIBI 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.