Drug Delivery and Drug Transport Modeling

Curriculum Vitea

Anthony McGoron, PhD

Of primary concern as new drugs are developed is that these drugs be specific in terms of their mechanism of action and their site of action. The common theme in my research is Drug Delivery and Drug Transport Modeling. Drug deliver research may involve the design of new drugs, or developing strategies to monitor and improve drug transport to target tissue.

Nuclear Medicine Imaging

We have examined the cellular uptake kinetics of novel radiolabeled chemicals that report regional metabolic variables of various organs or tumors. Tests are conducted in whole animal, isolated organ and isolated cell models. Computer models are used to estimate permeability and other transport properties of tracers from data from indicator dilution studies or images collected with a recently installed GE 4000AT SPECT camera. We are also developing novel drugs that will simultaneously diagnose (by imaging) and treat (by chemotherapy) tumors.

Planar Nuclear Medicine image of a rat showing Tc-99m concentrated in the heart, liver and bladder.

PET Glucose Metabolism and SPECT Perfusion Imaging

We are collaborating with scientists at the University of Miami School of Medicine to develop a tool for early diagnosis of the severity of traumatic brain injury in infants. We are measuring cerebral glucose metabolism (using Positron Emission Tomography, PET) and cerebral blood flow (using Single Photon Emission Computed Tomography, SPECT) correlated withhistochemical markers of cellular injury in a pig model. The goal is to determine from noninvasive diagnostic imaging early after injury which patients might benefit from aggressive treatment and which patients may recover without aggressive (and presumably dangerous) treatment.

SPECT Brain Blood Flow .................................PET Brain Glucose Metabolism

Respiratory Gated Positron Emission Tomography (PET)

PET glucose metabolism is often used to diagnose cancer since the fast growing highly metabolic tumor requires more energy than surrounding tissue. An accurate diagnosis requires a precise measure of the size of the tumor. But, due to the movement of the lungs during respiration, obtaining an accurate image of a lung tumor is difficult. We are developing instrumentation and imaging processing algorithms to gate the PET camera acquisition with the patient’s respiratory motion to reduce the lung motion artifacts. Recently PET has been combined with CT, which provides anatomy. In addition to supplying an anatomic reference for the PET metabolic image, the CT is also used to correct for attenuation of the PET to improve image quality. In order to apply CT attenuation correction to imagines of tissue in the lung, a computer-assisted automatic identification of lung lesions in the PET/CT images is also being developed to account for the movement of the lungs during the PET imaging.

PET and CT images from a GE Discover LS Hybrid PET/CT from Baptist Hospital of Miami. From left to right are the CT, PET, and PET/CT fused images.

Nanoscale Drug Design and Delivery for Improved Cancer Diagnosis and Therapy

Cancer is the second leading cause of death in the US, exceeded only by heart disease. Early detection of small primary tumors is critical for successful therapy and improved survival rates. Chemotherapy is often the first choice for treating many cancers. It is critical that the chemical be sequestered only in the target tissue at toxic concentrations so that nontarget tissue exposure is minimized. However, it is often difficult to ensure that the chemotherapy targets only the cancer and further that the chemical is localizing in the target tissue. Cancer cells easily take up extremely small (nano-sized) particles. New technologies are being developed to allow for the creation of complex nanoscale materials as drug delivery vehicles and sensors. Combining therapy with imaging has the potential to enhance the efficacy of treatment by ensuring and verifying that the drug reaches the target tissue, while minimizing nontarget tissue uptake. Light in the near-infrared (NIR) wavelength can easily pass through tissue and therefore, NIR fluorescent tracers can be used for imaging. Dyes that absorb energy may also release heat following exposure to the appropriate wavelength light and kill cancer cells. With a light sensitive dye incorporated into the drug delivery vehicle, therapy can be targeted since the drug won’t be activated with a laser until the drug has reached its intended target. The long term objective of this study is to develop a methodology of improved diagnosis and treatment of cancer by combining therapy and imaging in the same drug. The study is a collaboration of engineers, chemists, biologists, and clinicians with expertise in drug design, drug delivery modeling, and experimental models of cancer.

Selected Publications:

McGoron, A.J., M. Xuming, M.F. Georgiou, and J.W. Kuluz. Computer Phantom Study of Brain PET Glucose Metabolism Imaging Using a Rotating SPECT/PET Camera. Computers in Biology and Medicine. 2005, 35:511-531.

McGoron, A.J., J Franquiz. Emission Imaging: SPECT and PET. In Biomedical Technology and Devices Handbook. J. Moore and G. Zouridakis (eds), 2004.

Kassing, W.M, A.J. McGoron, S.R. Thomas, H.R. Elson, D.W. Pipes. Monte Carlo Calculations of Dose Distribution for Intramural Delivery of Radioisotopes Using a Direct Injection Balloon Catheter. Cardiovas Rad Med. 3:44-48, 2002.

McGoron, A.J., C.H. Clinton, M. Palascak, W.J. Claussen and R.S. Franco. Dehydration Of Mature And Immature Sickle Red Blood Cells During Fast Oxygenation/Deoxygenation Cycles: Role Of KCl Cotransport And Extracellular Calcium. Blood. 2000, 95:2164-2168.

McGoron, A.J., W.M. Kassing,S.R. Thomas, R.C. Samaratunga, R.G. Pratt, H.R. Elson, D.W. Pipes. Intravascular Irradiation Using Re-186 Liquid-Filled Balloon Catheters: Correlation Between Experimental and Theoretical Studies. Cardiovas Rad Med. 1999, 1:368-375.

McGoron, A.J., D Biniakiewicz, R.W. Millard, A. Kumar, S.C. Kennedy, N.J. Roszell, M. Gabel, C. Huth, R.A. Walsh, M.C. Gerson, Myocardial Kinetics of 99m-Technetium-Q Agents: Studies in Isolated Cardiac Myocyte, Isolated Perfused Rat Heart and Canine Regional Myocardial Ischemia Models. Investigative Radiology . 34:704-717, 1999.

Pratt, R.G., J. Zheng, B.K. Stewart, Y. Shiferaw, A.J. McGoron, R.C. Samaratunga and S.R. Thomas. Application of a 3D Volume Protocol for Mapping Oxygen Tension (pO2) in Perfluorocarbons at Low Field. Mag Res Med. 37:307-313, 1997.

McGoron, A.J., P.K. Nair, R.W. Schubert. Michaelis-Menten Kinetics Model of Oxygen Consumption by Rat Brain Slices Following Hypoxia. Annals Biomed Eng. 25:565-572, 1997.

Lee, M.T.B., C.J. Seliskar, W.R. Heineman and A.J. McGoron. Microelectrode Sensors for In Vivo Detection of Radiopharmaceuticals. J Am. Chem Soc. 119:6434-6435, 1997.

Recent Presentations at Scientific Meetings

Wang, J., McGoron, A.J., Byrne, Franquiz, J. Evaluation of a Novel PET Respiratory Gating Algorithm to Reduce Lung Tumor Blurring using the 4D NCAT Phantom. American Association of Physics in Medicine, 48th Annual Meeting. July 30-August 3, 2006

Wang, J., McGoron, A.J., Byrne, Franquiz, J. A Novel Respiratory Gating Design for Motion Tracking in PET/CT Imaging. Proceedings of 2006 Summer Bioengineering Conference. June 21-25, 2006.

Capille M, McGoron A, Georgiou M, Kuluz J, Sanchez P: Validation of SPECT CBF in Piglet Brain Injury by Registration of Reconstructed Microspheres. Radiological Society of North America (RSNA), (Scientific Assembly and Annual Meeting Program), Abstract #000WNM-p, 2004.

McGoron, A.J., J.W. Kuluz, M.F. Georgiou, P. Sanchez, M. Capille, and G.N. Sfakianakis. FDG Kinetics Imaging in Piglet Brain Using a Dual-Head Rotating SPECT/PET Camera. Proceeding of the Biomedical Engineering Society. Nashville, TN. October 1-4, 2003.

Capille, M. and A.J. McGoron. Radon Transform Sinogram Based Calculated Attenuation Correction for PET. Proceeding of the Biomedical Engineering Society. Nashville, TN. October 1-4, 2003.

McGoron, A.J., M.F. Georgiou, J.W. Kuluz, M. Zhou, P. Sanchez, and G.N. Sfakianakis. FDG Kinetics and Perfusion Imaging with a Dual-Head Rotating SPECT/PET Camera: Preliminary Animal Studies. Proceedings of the 2003 Summer Bioengineering Conference. Key Biscayne, FL. June 25-29, 2003.