Project Identifier: ORAU-95-95
Project Title:
Prospective Treatment Planning for Palliative Therapy of Bone Metastasis with Sn-117m
Principle Investigator:
Dr. James B. Stubbs
Principle Investigator's Institution: Oak Ridge Associated Universities
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project did not use human subjects in Fiscal Year 1995.
Explanation:
This project received no patient data during FY95.
Funding Sources:
No new funding from DOE was sought or obtained for this project. The above amount was redirected to specifically support this project.
This project operates under a CRADA, ORAU 94-001, with the private industry partners providing "in-kind" contributions only. No money was transferred to ORAU
Total Funding: $109,814
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 03, 1995
IRB Approval Number: 95
Number of Human Subjects in the Last Reporting Period for this Project: 5
(Reporting periods vary.)
Type of Human Subjects Involvement:
Not conducted by this contractor. Used records only.
Internal administration of radioactive substances to human subjects.
Not conducted by this contractor. Used records only.
Medical purposes - not by this contractor. (Body materials collected by another contractor, not by ORAU)
A. Objective
The purpose of this Cooperative Research and Development Agreement (CRADA) is to develop a radionuclide therapy treatment planning paradigm for patients receiving Sn-117m DTPA, a radiopharmaceutical for palliation of the pain associated with bone metastases. The resulting product will be a software package capable of computing radiation doses specific to individual patients.
NOTE - DOE funding is used solely for the purpose of analyzing and utilizing patient data for the purposes of developing the treatment planning software. The Oak Ridge Associated Universities (ORAU) will be receiving and utilizing patient data obtained by Brookhaven National Laboratory and the Veterans Affairs Medical Center in Tucson, Arizona, and will not be directly involved in subject recruitment, care, treatment or followup. Our use of these human data is no different, philosophically or in practice, from our routine use of human data for radiation dose estimations. Identifiable patient data will be protected to the extent allowable by law.
B. Methodology
The treatment planning paradigm consists of estimating the radiation absorbed doses to normal organs, including active bone marrow and metastatic lesions in the skeleton of individual patients. Radiation dose estimation for internally deposited radionuclides requires mathematical models of a patient's anatomy and of the temporal variation of the biodistribution and retention of the radiopharmaceutical.
To develop patient-specific dose estimates, two issues must be addressed: radiation transport modeling and biokinetic modeling. The radiation transport modeling will be performed by adapting preexisting anthropomorphic phantoms (Cristy and Eckerman, ORNL/TM-8381/V1, 1987) for use in an electron/photon transport code, MCNP-4A. To address the second issue, we will develop a biokinetic model of the activity uptake, retention, and washout in the various normal organs, lesions and routes of excretion. These data will be obtained from scintigraphy of the Sn-117m-labeled radiopharmaceutical in the patients for whom dose estimates are desired.
After mathematically modeling each patient's biokinetic data, the residence times are easily determined by integration of the equations simulating the biodistribution. Using a version of the MIRDOSE3 software specifically modified to estimate normal tissue and lesion doses, a dose estimate is calculated for that individual. From data describing maximum tolerated dose for normal tissues, it is a simple matter to determine the largest amount of activity that can be safely administered. Additionally, we can provide a more detailed report of the estimated active marrow dosimetry. This is accomplished by reporting the marrow dose in a new format: a histogram of the fraction of marrow receiving a certain amount of absorbed dose as a function of absorbed dose level. From this information, we may be able to estimate the fraction of the total marrow likely to receive myelotoxic amounts of absorbed dose.
By predicting the maximum tolerable dose to normal tissues and the fraction of marrow that may be suppressed, a scientific, systematic method of planning radionuclide therapy with Sn-117m will have been achieved.
C. Ionizing Radiation, Radioactive Materials, or Chemical Substances
Patients (after providing signed, informed consent) participating in this project will receive one or more injections of Sn-117m DTPA, a radiopharmaceutical. Patients may also receive a baseline bone scan using a Tc-99m-labeled radiopharmaceutical and one or more bone and chest x-rays. Patients will not be exposed to ionizing radiation, radioactive materials, or chemical substances, other than medications the patients are already taking at their acceptance for participation in this project or those diagnostic imaging procedures listed above, unless medically necessary.
D. Procedures Involving Human Subjects
Upon giving informed consent, medical histories and physical examinations will be obtained. Patients will then undergo routine blood tests and bone and chest x-rays (all routine for cancer patients). After completion of these initial assessments, patients will receive up to 35 mCi (most likely dose range 10-25 mCi) of Sn-117m DTPA via venipuncture. Blood and urine samples will be collected periodically over the next 6 months and scintigraphic images will be obtained over the 7 days following administration of the Sn-117m DTPA. Assessments of the duration and extent of pain relief will be verbally obtained until the patient is lost to followup.
The risks associated with the clinical protocol are those of mild to moderate myelotoxicity. Drops in white bIood cell and platelet counts most likely will occur, though the drops have not been severe enough to produce clinically significant myelotoxicity in Phase I and II clinical studies. Identifiable patient data will be protected to the extent allowable by law.