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Intravascular Radiation Detectors for the Detection of Vulnerable Atheroma

H. William Strauss, MD, FACC^_*,a,_*, Carina Mari, MD, Bradley E. Patt, PhD^,b and Vartan Ghazarossian, PhD^,a

^_* Section of Nuclear Medicine, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
Nuclear Medicine Program and Center for Molecular and Functional Imaging, University of California-San Francisco, UCSF, San Francisco, California
Gamma Medica Inc., Northridge, California
Imetrx Inc., Mountain View, California

Manuscript received August 30, 2005; revised manuscript received October 25, 2005, accepted November 4, 2005.

^_* Reprint requests and correspondence: Dr. H. William Strauss, Memorial Sloan Kettering Cancer Center, Clinical Director, Nuclear Medicine, 1275 York Avenue, New York, New York 10021 (Email: straussh{at}mskcc.org).

An intravascular catheter was developed to identify inflammation in coronary atheroma. Inflammation in atheroma is associated with large numbers of macrophages. These cells have increased metabolism, increased expression of chemotactic receptors, and a high frequency of apoptosis-associated phosphatidylserine expression. Each of these parameters can be identified in vivo using specific radiolabeled agents: metabolism can be identified with ¹⁸F fluorodeoxyglucose (FDG), receptor expression with ^99mTc monocyte chemotactic peptide-1, and apoptosis with ^99mTc annexin V. The locally increased concentration of these tracers is readily demonstrable in experimental lesions by ex vivo autoradiography; however, the small lesion size makes it difficult to identify atheroma in the coronaries with conventional imaging equipment. In contrast, with a radiation-sensitive catheter, optimized to sense charged particle rather than gamma or x-radiation, specific lesions could be identified and localized. Charged particle radiation is emitted as a byproduct of nearly all radioactive decay but is typically most abundant in radionuclides that decay by beta emission (either positrons or negatrons). Prototype catheters, using a plastic scintillator mated to an optical fiber, have been tested in the laboratory with the positron-emitting radiopharmaceutical ¹⁸FDG. The catheter had sufficient sensitivity to detect lesions concentrating nanocurie concentrations of ¹⁸FDG. Ex vivo experiments in apo-e^–/– mice confirmed the ability of the catheter to detect ¹⁸FDG in aortic lesions. These feasibility studies demonstrate the sensitivity of a beta-sensitive catheter system. Additional mechanical refinements are needed to optimize the system in anticipation of in vivo animal studies.

Abbreviations and Acronyms   FDG = fluorodeoxyglucose   MACE = major acute coronary events

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