Mark A. Green, Ph.D. Head, Division of Nuclear Pharmacy Professor of Industrial and Physical Pharmacy Phone: (765) 494-1445 Fax: (765) 496-3367 E-mail: magreen@purdue.edu Full directory listing

Specialization: Radiotracer methods in diagnostic imaging and radiotherapy. Biomedical imaging techniques for non-invasive assessment of pharmacokinetics, pharmacodynamics, and therapeutic outcome(s).  Positron emission tomography (PET). Radiopharmaceutical chemistry.

Education

Research: Radiotracer methods in diagnostic imaging and radiotherapy. Biomedical imaging techniques for non-invasive assessment of pharmacokinetics, pharmacodynamics, and therapeutic outcome(s).  Positron emission tomography (PET). Radiopharmaceutical chemistry.

My group's research focuses on the design, synthesis, and evaluation of new radiopharmaceuticals. The practice of nuclear medicine is based on the use of such radioactive drugs to obtain images of the human body. Employing a camera that detects gamma-photons leaving a patient's body, the physician can non-invasively visualize and monitor internal radiotracer distribution and pharmacokinetics. The clinical utility of such methods rests on availability of radiopharmaceuticals that can serve as selective and specific probes of regional tissue pathophysiology.

We are primarily exploring applications for short-lived metallic radionuclides that have been selected for investigation because they offer unique and/or attractive nuclear properties. A number of such gamma-emitting radionuclides (e.g., Ga-67, In-111, and Tc-99m) are already in widespread clinical use because they: (i) offer excellent nuclear properties for imaging, and (ii) can be chemically incorporated into radiopharmaceuticals for diverse clinical applications. Other metallic radionuclides, such as generator-based copper-62 and gallium-68, appear promising as tools that could facilitate more widespread clinical use of positron emission tomography (PET) in diagnostic imaging. Still other metallic radionuclides that emit both gamma photons and Beta-particles (such as 64Cu and 67Cu) are attractive for clinical applications where they could be exploited for both imaging and radiotherapy.

Our research in radiopharmaceutical chemistry encompasses a broad spectrum of laboratory activities, beginning with the synthesis and characterization of novel chelating ligands and metal complexes using conventional laboratory techniques. Subsequently, the chemistry is scaled down to the minute concentrations of metal radionuclide found in radiopharmaceutical preparations (typically 10M^-8 - 10^-12 M). These new agents are then evaluated in animal models to directly determine radiotracer biodistribution and pharmacokinetics, and to define the compound's chemical fate in vivo.

The resulting biological data is used in elucidation of structure-activity relationships, as well as providing a basis for assessing potential clinical utility. The best compounds identified in initial screening are subsequently examined in more sophisticated models that allow, under a variety of physiological conditions, direct evaluation of the relationship between tracer uptake and specific aspects of tissue pathophysiology. For promising tracers identified in this manner, we have productive collaborative relationships with a number of clinical investigators that allow additional preclinical and clinical assessment of radiopharmaceutical performance.

Our current research efforts include development of tracers for the study of regional cerebral, myocardial, renal, and tumor blood flow, as well as investigation of general strategies for selective radiotracer targeting to neoplastic tissue).

Representative Publications

N. G. Haynes, J. L. Lacy, N. Nayak, C. S. Martin, D. Dai, C. J. Mathias, and M. A. Green. "Performance of a Zn-62/Cu-62 Generator in Clinical Trials of the PET Perfusion Agent 62Cu-PTSM," J. Nucl. Med. 41, 309-314 (2000).

C. J. Mathias, D. Hubers, P. S. Low, and M. A. Green. "Synthesis of [^99mTc]-Tc-DTPA-Folate and Its Evaluation as a Folate-Receptor-Targeted Radiopharmaceutical," Bioconjugate Chemistry 11, (in press) (2000).

V. Sharma, A. Beatty, S. P. Wey, L. Bass, C. L. Crankshaw, M. A. Green, M. A. J. Welch, and D. Piwnica-Worms. "Novel gallium(III) complexes transported by MDR1 P-glycoprotein: potential PET imaging agents for probing P-glyoprotein-mediated transport activity in vivo," Chemistry and Biology. 7, 335-343 (2000).

C. J. Mathias, S. Wang, P. S. Low, D. J. Waters, and M. A. Green. "Receptor-Mediated Targeting of 67Ga-Deferoxamine-Folate to Folate-Receptor-Positive Human KB Tumor Xenografts," Nucl. Med. Biol. 26, 23-25 (1999).

C. J. Mathias, S. Wang, D. J. Waters, J. J. Turek, P. S. Low, and M. A. Green. "Evaluation of ¹¹¹In-DTPA-Folate as a Potential Folate-Receptor-Targeted Radiopharmaceutical," J. Nucl. Med. 39, 1579-1585 (1998).

M. A. Green. "Copper-6 2 Radiopharmaceuticals for Diagnostic Imaging with Positron Emission Tomography (PET)," Transition Metal Chemistry 22, 427-429 (1997).

J. K. Lim, C. J. Mathias, and M. A. Green, "Mixed Bis(thiosemicarbazone) Ligands for Preparation of Copper Radiopharmaceuticals: Synthesis and Evaluation of Tetradentate Ligands Containing Two Dissimilar Thiosemicarbazone Functions," J. Med. Chem., 40, 132-136 (1997).

S. Wang, R. J. Lee, C. J. Mathias, M. A. Green, and P. S. Low, "Synthesis, Purification, and Tumor Cell Uptake of ⁶⁷Ga-Deferoxamine-Folate Conjugate, a Potential Radiopharmaceutical for Tumor Imaging," Bioconjujate Chemistry, 7, 56-62 (1996).

C. J. Mathias, S. Wang, R. J. Lee, D. J. Waters, P. S. Low, and M. A. Green, "Tumor-Selective Radiopharmaceutical targeting via Receptor-Mediated Endocytosis: Evaluation of a Gallium-67 Labeled Folate-Deferoxamine Conjugate," Journal of Nuclear Medicine, 37, 1003-1008 (1996).

P. Herrero, J. J. Hartman, M. A. Green, C. J. Anderson, M. J. Welch, J. Markham, and S. R. Bergmann, "Assessment of Regional Myocardial Perfusion with Generator-Produced 62Cu-PTSM and PET in Human Subjects," Journal of Nuclear Medicine, 37, 1294-1300 (1996).

Curriculum Vitae

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