Trial Information

A Pilot Study of Tc-94m Sestamibi PET MDR Imaging

Background:

- A pilot study of PET imaging with Tc-94m sestamibi to assess activity of the multidrug
transporter, MDR-1/P-glycoprotein, an ATP-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 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 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.