PET Imaging With Tc-94m Sestamibi to Assess Resistance to Chemotherapy
| Status: | Completed |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 8/18/2017 |
| Start Date: | May 16, 2004 |
| End Date: | April 14, 2014 |
A Pilot Study of Tc-94m Sestamibi PET MDR Imaging
Background:
- Tc-94m sestamibi is a radioactive imaging drug approved by the Food and Drug
Administration to help photograph and study bodily functions.
- Tc-94m sestamibi accumulates in tumor cells and is eliminated from them in much the same
way that some chemotherapy drugs are eliminated from cancer cells in patients with drug
resistance.
- P-glycoprotein is a protein found on the surface of some cancer cells. The protein
causes the cells to pump out, or reject, some types of chemotherapy drugs.
P-glycoprotein also makes the cells reject sestamibi.
- Some drugs, including a drug called tariquidar, may block the pumping action of
P-glycoprotein, giving the chemotherapy more time to work. Tariquidar can also help
sestamibi stay in the cells longer.
Objectives:
-To evaluate the use of sestamibi for determining if chemotherapy is being rejected and if
enough of the blocking drugs are present to stop the rejection.
Eligibility:
-Patients18 years of age and older with a tumor 2 cm or larger who are enrolled in or are
eligible for enrollment in an active National Cancer Institute treatment protocol.
Design:
- Patients have two scans, one before receiving any drugs and a second 1-2 hours after
receiving tariquidar. The second scan is done 72 or more hours after the first. For both
scans, Tc-94m sestamibi is injected into a vein and a series of pictures are taken with
an imaging camera called a PET (positron emission tomography) scanner. The pictures show
where the sestamibi distributes in the body and monitors the effects of tariquidar on
drug resistance. Blood samples are collected during the scan to examine the effect of
tariquidar on P-glycoprotein in normal cells.
- Some patients may be asked to undergo a tumor biopsy to test for the presence of the
P-glycoprotein on their cancer cells. This will be requested only in patients whose
tumor is easily accessible and in whom a biopsy can be done with minimal risk.
- Tc-94m sestamibi is a radioactive imaging drug approved by the Food and Drug
Administration to help photograph and study bodily functions.
- Tc-94m sestamibi accumulates in tumor cells and is eliminated from them in much the same
way that some chemotherapy drugs are eliminated from cancer cells in patients with drug
resistance.
- P-glycoprotein is a protein found on the surface of some cancer cells. The protein
causes the cells to pump out, or reject, some types of chemotherapy drugs.
P-glycoprotein also makes the cells reject sestamibi.
- Some drugs, including a drug called tariquidar, may block the pumping action of
P-glycoprotein, giving the chemotherapy more time to work. Tariquidar can also help
sestamibi stay in the cells longer.
Objectives:
-To evaluate the use of sestamibi for determining if chemotherapy is being rejected and if
enough of the blocking drugs are present to stop the rejection.
Eligibility:
-Patients18 years of age and older with a tumor 2 cm or larger who are enrolled in or are
eligible for enrollment in an active National Cancer Institute treatment protocol.
Design:
- Patients have two scans, one before receiving any drugs and a second 1-2 hours after
receiving tariquidar. The second scan is done 72 or more hours after the first. For both
scans, Tc-94m sestamibi is injected into a vein and a series of pictures are taken with
an imaging camera called a PET (positron emission tomography) scanner. The pictures show
where the sestamibi distributes in the body and monitors the effects of tariquidar on
drug resistance. Blood samples are collected during the scan to examine the effect of
tariquidar on P-glycoprotein in normal cells.
- Some patients may be asked to undergo a tumor biopsy to test for the presence of the
P-glycoprotein on their cancer cells. This will be requested only in patients whose
tumor is easily accessible and in whom a biopsy can be done with minimal risk.
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.
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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