Medical Physics Seminar – Monday, March 11, 2013
Imaging oncogenic pathway signaling with metal-based radiotracers
Jason P. Holland, D.Phil (guest of Dr. Weibo Cai)
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Department of Radiology, Harvard Medical School, Boston, MA 02114 USA
Keywords: PET imaging, 89Zr, monoclonal antibodies, oncogenes, c-MYC, PTEN, transferrin, prostate cancer, PSMA, PSA.
In recent years, the nuclear medicine and imaging communities have focused attention on the development of “molecular imaging agents†for identification of target-rich sites that purport a relationship to clinically relevant parameters. For example, elevated expression levels of numerous protein biomarkers like epidermal growth-factor receptor (EGFR), Her2/neu and prostate-specific membrane antigen (PSMA) have been validated as imaging/therapeutic targets for various cancers. Yet in spite of much preclinical success, translation of new imaging agents has been slow, and the clinical value of such radiotracers remains in contention.
While the repertoire of targeted chemotherapies for cancer continues to expand rapidly, there are virtually no non-invasive technologies that measure the degree of signaling through oncogenic pathways. In this presentation, we explore how an understanding of clinical requirements helped reshape our initial radiotracer program. From a foundation in the design of targeted molecular imaging agents with zirconium-89 radiolabelled monoclonal antibodies for monitoring therapy, we discover how a combination of new and old technologies can be exploited to produce the next generation of radiotracers reporting on functional oncogenic signaling status.
References:
J.P. Holland et al. Nucl. Med. Biol., 2009, 36, 729-739.
J.P. Holland et al. J. Nucl. Med., 2010, 51(8), 1293-1300.
J.P. Holland et al. Mol. Imaging, 2010, 9(1), 1-20.
J.P. Holland et al. PLoS ONE, 2010, 5(1), e8859.
J.P. Holland et al. Nature Med., 2012, 18, 1586-1591.
†Email: holland.jason@mgh.harvard.edu. Tel: +1.617-726-6107