PET Imaging With Tc-94m Sestamibi to Assess Resistance to Chemotherapy

Background:

• A pilot study of PET imaging with Tc-94m sestamibi to assess activity of the multidrug transporter, MDR-1 (Multi Drug Resistance Protein 1)/P-glycoprotein, an ATP (adenosine 5'-triphosphate)-binding cassette protein that transports drug out of the cell, thereby reducing intracellular drug accumulation.
• Tariquidar is a safe, nontoxic antagonist of P-glycoprotein. Previous studies demonstrated that tariquidar increased retention of the radioimaging agent, Tc99 sestamibi in normal liver and in a subset of tumors. These studies were limited by the semiquantitative nature of total body imaging by conventional radionuclide scintigraphy
• In collaboration with the Clinical Center Nuclear Medicine Department, a PET imaging agent has been developed, Tc-94m sestamibi, and the FDA (Food and Drug Administration) has granted approval for its use in humans.

Objectives:

-To evaluate the feasibility of Tc-94m sestamibi as a PET imaging agent, which should allow greater resolution and quantitation and thereby make possible direct quantitative comparisons of tumor uptake before and after treatment with a P-glycoprotein antagonist.

Eligibility:

• Patients over 18 years of age, who are eligible for, or have completed enrollment in an active NCI (National Cancer Institute) protocol for treatment of cancer.
• Negative pregnancy test within 24 hrs of Tc-94m injection.
• An index lesion greater than 2cm will be required to optimize the PET images.
• Prior treatment with a P-glycoprotein antagonist is allowed.

Design:

• Designed as a feasibility study. Patients meeting the eligibility criteria and signing informed consent will undergo a PET sestamibi imaging scan in the Department of Nuclear Medicine. Seventy-two hours later, a dose of tariquidar will be administered before a repeat imaging study.
• Blood will be obtained for analysis of the pharmacokinetics of Tc-94m sestamibi, and for isolation of peripheral blood mononuclear cells to assay P-glycoprotein inhibition in circulating CD56+ cells. These assessments are needed to confirm the impact of tariquidar on P-glycoprotein in normal cells - for example, those involved in drug excretion and in circulating mononuclear cells. These results will then be used to inform the findings in the PET imaging study.
• Fifteen patients will be enrolled and pairwise comparisons will be made between the sestamibi residence times in tumor, normal liver, kidney, and heart. All comparisons are noted to be exploratory.

• INCLUSION CRITERIA:

Patients must be eligible for enrollment in an active NCI (National Cancer Institute) protocol for treatment of cancer.

Patients greater than or equal to 18 years old.

Performance Status ECOG (Eastern Cooperative Oncology Group) 0 - 2.

Patients must be able to give informed consent.

Women of childbearing potential must have a negative pregnancy test within 24 hrs of Tc-94m injection.

Patients who have previously received tariquidar will be eligible, since no study has systematically shown loss of MDR-1 (Multi Drug Resistance Protein 1)/Pgp expression in tumors following exposure to both tariquidar and an anticancer agent.

An index lesion greater than 1.5 cm will be required to optimize the PET (positron emission imaging) images.

Exclusion criteria

Patients who are pregnant or breast-feeding will not be enrolled in order to prevent radiation exposure in the developing fetus or infant.

Patients weighing greater than 136 kg (the weight limit for the scanner table).

Patients having only tumor sizes less than 1.5 cm will be excluded.

HIV (human immunodeficiency virus) positive patients will be excluded to prevent potential drug interactions between tariquidar and antiretroviral agents.