This technology is being used and developed in two separate research projects (i) Antisense Oligonucleotides for PET Imaging of Gene Expression, sponsored by the DOE Office of Biological and Energy Research, Molecular Nuclear Medicine Program , and (ii) Visual Servoing Optical Microscopy for Quantification of MultiDrug Resistance in Living Cells, sponsored by the University of California Industry-University Cooperative Research Program (IUCRP). Initial development of VSOM took place under a project entitled Visual Servoing for Optimization of Anticancer Drug Uptake in Human Breast Cancer Cells sponsored by the Department of Defense, Breast Cancer Research Program, under the U.S. Army Medical Research and Materiel Command, DAMD17-98-1-8177.

In the first project, PET imaging agents are being developed that are based on custom-synthesized, artificial DNA and RNA fragments called antisense oligonucleotides (AS-ONs). The objective is to extend nuclear medicine (Positron Emission Tomography, or PET) to the cellular level by developing new tools for imaging gene expression in humans. A companion grant, entitled Strategies for Imaging Gene Expression with PET is underway in the Life Sciences Department of Nuclear Medicine and Functional Imaging. To fully explore the potential of AS-ON imaging agents, an infrastructure has been developed for intelligent design and modification of AS-ON agents and delivery vehicles. VSOM is just one component of a multi-step development process that brings together and leverages LBNL’s expertise in automation, computer science, medical imaging, and gene technology. This project is a joint effort with Dr. Bahram Parvin of the LBNL Computational Research Division, Imaging and Informatics Group. In the second project, (also a collaboration with Dr. Parvin) new in vitro capabilities for imaging and characterizing multidrug resistance in living, human breast cancer cells are being developed and demonstrated.

Dr. Callahan has also performed and published fluorescence microscope studies performed on living human brain tumor cells. The objective of this research was to enhance the preferential uptake and retention of a boronated protoporphyrin (BOPP) in human brain tumors relative to normal tissue. BOPP is a compound that may prove useful in the cancer radiation treatment known as boron neutron capture therapy (BNCT) In BNCT patients are treated with a boronated compound that accumulates in brain tumors. Patients are then irradiated with neutrons.

As a biophysicist, Dr. Callahan has used nuclear magnetic resonance (NMR), fluorescence, and circular dichroism (CD) spectroscopy to study the conformation of DNA and DNA analogs designed for use as antisense anticancer and antiviral agents. He has also investigated magnetic resonance imaging (MRI) techniques designed to optimize differences in the intracellular water of normal and cancer cells. His publications in the field of fluorescence microscopy include the mapping and quantitation of human papilloma virus (HPV) integration sites in human cervical cancer, and multicolor, 3D studies of chromosome organization in human lymphocytes.