Determination of cellular level kinetics of fluorine-18 tagged phenylalanine and evaluation of infusion protocols

The treatment of cancer in humans continues to be a significant technological and medical challenge. Currently the cause of death in one out of five persons is cancer. The challenge for medical treatment and ultimately remission of cancer is one of selective cell killing. Most methods of cancer treatment include significant damage to normal tissue resulting in necrosis and complications. The most promising treatment methods selectively affect the cancerous cells. The treatment of otherwise inoperable cancers such as glioblastomas and certain forms of melanoma have historically been approached with Boron Neutron Capture Therapy (BNCT). This method uses boron compounds that are preferentially absorbed in cancer tissue followed by patient irradiation with neutrons. Boron's high probability of absorption of neutrons and its subsequent release of energy to critical cellular structures result in selective cell killing.; Two important issues concerning BNCT are: to understand the biokinetics of the boron compound and its distribution in the various regions within the brain tissue and to improve the infusion protocols of the BNCT pre-treatment planning which could help clinical trials be more effective.; Methods for the determination of cellular level kinetics of F-18-Tagged Phenylalanine are used to describe the pharmaceutical distribution within the human brain which includes evaluating the pharmacokinetic parameters, evaluating various compartmental models, transferring from bolus infusions to continuous infusions and evaluating infusion protocols. A second order compartmental model is used to analyze the data from Positron Emission Tomography (PET) scans. These data are fitted to a double exponential model to determine the eigenvalues of each region of interest, which are used in the determination of the rate constants and the evaluation of the PET model responses. In addition, the data are fitted to a second order compartmental model to estimate the rate constants that describe the transfer of the boron compound in the various compartments of the particular region of interest. MATLAB and MODELMAKER are used to estimate these parameters. These rate constants are used in simulation methods to transfer from bolus infusion to continuous infusion and to evaluate the various infusion protocols in an effort to enhance the efficacy of BNCT. Both single and multiple infusions are used, but results show that a single infusion is the most effective. Best results were achieved with a single infusion of the boron compound for a period of time ranging from fifteen to twenty hours followed by a one to two hour wait period before irradiating in the neutron beam.