USDOE Human Subjects Research Database, Fiscal Year 1999

University of Tennessee Medical Center-Knoxville

Public Information Contact:

Dr. George W. Kabalka
University of Tennessee Medical Center
1924 Alcoa Highway
Knoxville, TN 37920-

Phone: 615-544-9670
Fax: 615-544-8883
E-mail: kabalka@utk.edu

Institutional Review Board (IRB):

Human Subject Projects:

Number of Human Subjects projects reported: 1

UTMC-93-IRB-0555

"An Evaluation of Fluorine-18 Labeled BPA-F in Patients with Glioblastoma Multiforme Using Positron Emission Tomography (PET)"

Project Identifier: UTMC-93-IRB-0555

"An Evaluation of Fluorine-18 Labeled BPA-F in Patients with Glioblastoma Multiforme Using Positron Emission Tomography (PET)"

Principal Investigator: Dr. George W. Kabalka, University of Tennessee Medical Center-Knoxville

Project started in: 1993

Project Funding Information:

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$65,000.00 (Est.) for: Fiscal Year 1999
Three patients with GMB were studied during this reporting period. A total of five 3F-18-BPA PET scans were performed.

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 02/19/99
IRB approval number: 0555/0737

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects: Fiscal Year 1999 (10/1/98-9/30/99)

Type(s) of Human Subjects Involvement:

External use of ionizing radiation on human subjects:

• For clinical research

Internal administration of radioactive substances to human subjects:

• For clinical research

Internal use of chemical substances (solid, liquid, or gas) on human subjects:

• For clinical research

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excretia, etc):

• Using bodily materials collected specifically for this project.

Use of personally identifiable data from questionnaires, surveys, or epidemiological studies:

• Using data collected from subjects specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

The overall incidence of glioblastoma multiforme (GBM) in the United States has been estimated to be approximately 7,000 new cases per year. The treatment of GBM is problematic. Most patients undergo a surgical "debulking" followed by radiation therapy. A successful surgical approach is improbable in cases with diffuse and infiltrating growth of the tumor. Furthermore, the low tolerance of the normal brain tissue limits the delivery of tumor-effective radiation doses. Chemotherapy has been shown to be ineffective. As a result, the median survival time is less than 12 months. The overall prognosis for a patient suffering from GBM remains dismal.

Boron neutron capture therapy (BNCT) represents a promising alternative for selective radiation therapy of such tumors. The specific aims in this study are: to evaluate 4-Borono-2[18F] Fluoro-D, L-Phenylalanine-Fructose Complex [18F]BPA-F with the use of positron emission tomography (PET); to measure the pharmacokinetics of [18F]BPA-F and to examine if the GBM and/or normal brain accumulation of [18F]BPA-F changes as a result of surgery; to evaluate the accumulation of [18F]BPA-F in the residual tumor for potential BNCT; and to evaluate the use of [18F]BPA-F imaging for measuring the response to BNCT.

All patients will be referred for PET brain scans on the basis of clinical indication with a strong suspicion for GBM. Following the brain scan, a whole body PET scan will also be obtained, if the patient can tolerate it, in order to gather information on the extracranial distribution of the BPA. The patients shall be 18 years of age or older. All patients will have undergone physical, neurologic, fundoscopic, and visual field examinations, as well as x-ray computerized tomography (CT) and/or magnetic resonance imaging (MRI) studies of the brain within one week to ten days of the PET examination. All tumors will be confirmed histologically. The biopsies will be done after the PET scan to avoid non-specific biochemical changes secondary to the surgical procedure. A second PET scan, including brain and whole body, will be done 4 to 6 weeks after the craniotomy, if possible.

A transmission scan will be done using an external ring source containing germanium-68 for the purpose of acquiring data for image attenuation correction. Following the transmission scan, patients will be given fluorine-18 labeled BPA-F by intravenous injection. The average dose to be given is 0.15 millicurie (mCi) per Kilogram (Kg) of body weight. PET imaging of the brain will begin immediately after administration of the radiolabeled BPA-F. Scans will be carried out using the 47 slice tomograph which provides a spatial resolution of approximately 5 millimeters in 7 millimeter slices. Images of the BPA-F utilization will be analyzed quantitatively for selected regions of interest.

Patients will participate with informed consent. All information gathered in this study will be treated confidentially and the privacy of the research subject will be protected. Patients will receive nothing by mouth (NPO) for at least 4 hours prior to the scan. Each patient will have a venous line kept open by a 0.9% Sodium Chloride for Injection, United States Pharmacopeia (U.S.P.) drip through an 18 to 20 gauge needle for adequate bolus administration of the radiotracer. Vital signs will be monitored prior to, during, and after the PET scan.

Participation in the PET study involves exposure to radiation. The estimated total body radiation dose that the patient may receive from 2 x [18F]BPA-F injections (10 mCi/injection) is 0.94 rem or approximately 19% of the annual radiation dose allowed to a radiation worker in the course of his/her normal work activities. This radiation dose is not expected to produce any harmful effects.

Adverse effects with BPA-F have been generally non-complicating. Investigators at Idaho State University have studied the acute toxicity of intravenously administered BPA-F at very high doses. The investigators found that intravenous administration of BPA-F doses up to 3000 mg (BPA)/kg appeared to be well tolerated when delivered over a 1-hour infusion period to minimally stressed rats.

Arterial or venous blood samples not to exceed a total volume of 60 mL may be drawn during a period of 60 to 90 minutes. The patient may have some discomfort in the arm. There is a possibility of the artery being lacerated during cannulation; however, the probability of this occurring is extremely slight. There is also a chance that arterial spasm may occur, which would make the patient's hand become cold and painful. If this occurs, the physician may treat the spasm with lidocaine or stop the procedure. Rarely, a clot may form and require surgical removal. A small collection of blood can occur when the tube is removed, and a bruise may occur. Overall, the complications described are unlikely to occur.

Patients participating in this study may be required to endure up to 4 hours of PET imaging procedures. The PET procedures have been broken into two 2-hour segments, with intermittent ambulation.

The purpose of this preliminary investigation is to evaluate whether PET using [18F]BPA-F can be used to study the biodistribution of [18F]BPA-F. The results of this PET study will not be used to guide the therapy of the involved patients. Hence, involved patients will receive no direct benefit from this study. Their participation may result in an improved understanding of the pharmacokinetics of [18F]BPA-F in patients with GBM and perhaps improve therapy planning.