Analyzing Breast Tumor Permeability
E. Wiener,* M. Aref, J. Wang
National Institutes of Health, R29-CA61918-01

Tumors make their own blood vessels by secreting molecules that stimulate angiogenesis, such as vascular endothelial growth factor (VEGF). This molecule was also called vascular permeability factor because it increased the permeability of these blood vessels to macromolecules such as proteins and polymers. We have developed magnetic resonance imaging (MRI) contrast agents which allow for the preparation of agents with discrete sizes. We are using MRI and these contrast agents to determine if differences in vascular permeability can be used to differentiate benign from malignant breast tumors.

Characterizing Dual Magnetic Resonance Imaging and Boron Neutron Capture Therapy Reagents
E. Wiener,* N. Pederson
National Institutes of Health, PHS 2P41 RR 05964-06

Neutron capture therapy (NCT) is a binary technique that delivers a nonradioactive agent to the tumor followed by neutron irradiation and conversion of the agent into a radioactive compound. To predict the efficacy of the treatment, one must run dosimetic calculations. This implies an a priori knowledge of the drug concentration. One technique uses a method based on the tumor enhancement achieved with gadolinium labeled derivatives and magnetic resonance imaging (MRI). This requires an understanding of the magnetic properties of the agents under physiological conditions. We are characterizing a gadolinium labeled carbon derivative for dual MRI and NCt applications.

Medical Dosimetry Planning and Determination
T. Djemil,* J. Stubbins,* M Garada
Covenant Medical Center

This project is to develop efficient methods for planning patient dosimetry for radiation oncology applications using accelerator beams. The work is carried out in conjunction with a local hospital and the applications are clinical in nature.

Probing the Order within Neonatal Heart Rate Variability
R. Uddin,* J. R. Moorman,* M. P. Griffin
University of Virginia

Reason(s) for the fall of heart rate variability (HRV) during neonatal illness is being investigated by analyzing the nature and amounts of order in RR interval time series from 25 neonatal ICU patients with a spectrum of clinical illness severity. We are measuring predictability (deviation of predicted intervals from observed), and regularity (measured as approximate entropy) of RR interval time series with different degrees of HRV. These measures are being used to investigate the nature of order in the data as HRV changes.

Structure and Growth of Tumors
R. Uddin,* I. Saeed
Medical College of Virginia

We are simulating the growth of a tumor to predict the formation of the capsule and/or the lobes that appear in certain tumors. One-dimensional simulations in Carterian, cylindercal, and spherical geometries show interesting coordinate-dependent effects. Realistic generation terms lead to lobular structure. Simulations in multidimensions are being performed.

Targeting Ion-Chelate Complexes to Tumors and Tumor Cells
E. Wiener,* S. Konda, M. Aref, J. Wang
National Institutes of Health, R29-CA61918-01

Ion-chelate complexes have many applications in tumor diagnosis and therapy. Radioactive isotopes of technetium, yttrium, indium, and samarium offer applications in radioscintography and radiotherapy. Gadolinium has applications in magnetic resonance imaging and neutron capture therapy. We have attached ion-chelate complexes to Starburst? dendrimers. Folic acid was attached to these polymers. They specifically bind to tumor cells that express the high affinity folate receptor. We are using these polymers to diagnose and treat tumors that express this receptor in vivo. Tumors of epithelial origin express this receptor. These include 90% of ovarian tumors, ependymomas, and choroid plexus tumors.