Usefulness of 99mTc-Sestamibi Scintigraphy in Suggesting the Therapeutic Effect of Chemotherapy against Gastric Cancer

Abstract

Purpose: Imaging with 99m Tc-sestamibi ( 99m Tc-MIBI) has been used to assess 170-kDa P-glycoprotein (P-gp) expression and predict chemotherapy responses in several types of malignancy, such as breast and lung cancers. The purpose of this study was to evaluate the relationship between 99m Tc-MIBI accumulation in tumors and sensitivity to chemotherapy in gastric cancer patients.Experimental Design: Thirty-six patients with advanced gastric cancer underwent 99m Tc-MIBI scintigraphy before chemotherapy. Patients also underwent endoscopic biopsy, and the expression of P-gp or multidrug resistance-associated protein was analyzed by immunohistochemical staining. The relationship between the accumulation of 99m Tc-MIBI in tumors and responses to chemotherapy with 5-fluorouracil/cis-diamminedichloroplatinum(II) or epirubicin was examined.Results: Higher accumulation of 9m Tc-MIBI in tumors was observed in 25 and 23 of 36 gastric cancer patients at the early (30 min) and delayed (120 min) images, respectively. Accelerated accumulation of 99m Tc-MIBI negatively correlates with increased expression of P-gp, but not of multidrug resistance-associated protein, as determined by immunohistochemistry in gastric cancer tissues. The response rate to 5-fluorouracil/cis-diamminedichloroplatinum(II) chemotherapy in patients with high 99m Tc-MIBI accumulation (15.4%) was much lower than that in patients with low 99m Tc-MIBI accumulation (54.5%). In contrast, patients with high 99m Tc-MIBI accumulation show a higher response rate (41.7%) to chemotherapy with epirubicin, which is known to be a substrate of P-gp transporter. Conclusions:99m Tc-MIBI scintigraphy is useful to suggest the responses to chemotherapy of patients with advanced gastric cancer.

PET and SPECT in Cancer Theragnostics

“…In particular, 99m Tc-Sestamibi has been tested in patients with different types of cancer including breast cancer, lung cancer, gastric cancer, epatocellular carcinoma, osteosarcoma, lymphoma and myeloma. [139][140][141][142][143][144] A reduced net uptake or an enhanced efflux of the tracer were associated with high levels of Pgp in tumors. Furthermore, these imaging parameters were reported to predict tumor response to subsequent chemotherapy in patients with breast cancer, [145][146][147][148] osteosarcoma, 149 and myeloma.…”

Oncologic Applications of Sestamibi: In Vivo Imaging of Multi-Drug Resistance

“…There are limited encouraging in vitro or in vivo experiences concerning the hepatic neoplasms and advanced gastric cancer [90][91][92]. The association of enhanced 99m Tc-Sestamibi efflux in 99m Tc-Sestamibi SPECT with overexpression of P-gp in hepatocellular carcinoma has been observed to be strong [93].…”

The Translational Research Working Group Developmental Pathway for Image-Based Assessment Modalities

“…One mechanism that tumor cells use to escape the cytotoxic effects of chemotherapeutic agents is to increase the expression of P-glycoprotein. Therefore, as physicians began to explore the potential value of the commercially available sestamibi as a tumor imaging agent, it also became apparent that sestamibi could give an indication of the P-glycoprotein activity in tumors and, thereby, predict which tumors were most likely to express multidrug resistance (6). This new oncologic use of sestamibi has matured, and has been studied extensively at the cellular and molecular level, but it has not been clinically optimized as rigorously as would be desirable.…”