Abstract

99mTc-methoxyisobutyl isonitrile (MIBI) is a suitable transport substrate for the multidrug resistance gene prod-uct P-glycoprotein (P-gp) and widely used for tumor imaging. Bromocriptine has been shown to inhibit the ATPase activity and the function of P-gp. We hypothesized that bromocriptine could promote the accumulation of MIBI by inhibiting P-gp activities, a feature that can be taken advantage of for enhancing 99mTc-MIBI imaging. In the cur-rent study, we sought to investigate whether bromocriptine enhanced the uptake of 99mTc-MIBI in hepatocellular carcinoma patients. Sixty primary hepatocellular carcinoma patients received 99mTc-MIBI single photon emission computer tomgraphy (SPECT) prior to surgery. 99mTc-MIBI SPECT was performed 15 and 120 min after injection of 20 mCi 99mTc-MIBI, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of 99mTc-MIBI were obtained. In addition, a second 99mTc-MIBI SPECT was performed according to the same method 48 h after bromocriptine administration. We found that, prior to bromocriptine administration, significant MIBI uptake in tumor lesions was noted in only 10 (16.7%, 10/60) patients with hepatocellular carcinoma. No significant MIBI uptake was observed in the tumor lesions of the remaining 50 (83.3%, 50/60) hepatocellular carcinoma patients. Following bromocriptine administration, all the patients without apparent MIBI uptake demonstrated significant MIBI uptake on 99mTc-MIBI SPECT (P < 0.05). Our findings indicate that bromocriptine enhances the uptake of 99mTc-MIBI in patients with hepatocellular carcinoma.

Highlights

  • Until now, the main obstacle to a successful cure of cancer has been the intrinsic or acquired resistance of the neoplastic cells to a variety of structurally and functionally heterogeneous anticancer agents, which is named multidrug resistance (MDR)

  • Analysis of 99mTc-methoxyisobutyl isonitrile (MIBI) single photon emission computer tomgraphy (SPECT) imaging data of these hepatocellular carcinoma patients revealed that, prior to bromocriptine administration, significant MIBI uptake in tumor lesions was noted in only 10 (16.7%, 10/60) patients with hepatocellular carcinoma

  • No significant MIBI uptake was observed in the tumor lesions of the remaining 50 (83.3% 50/60) hepatocellular carcinoma patients

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Summary

Introduction

The main obstacle to a successful cure of cancer has been the intrinsic or acquired resistance of the neoplastic cells to a variety of structurally and functionally heterogeneous anticancer agents, which is named multidrug resistance (MDR). All the patients without apparent MIBI uptake demonstrated significant MIBI uptake on 99mTc-MIBI SPECT (P < 0.05). Our findings indicate that bromocriptine enhances the uptake of 99mTc-MIBI in patients with hepatocellular carcinoma. Recent studies have revealed that 99mTc-MIBI is a suitable transport substrate for P-gp and may provide additional information about the P-gp status of tumor cells[17,18].

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