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Technetium-99m-N1-(2-Mercapto-2-Methylpropyl)-N2-(2-Propargylthio-2-Methylpropyl)-1,2-Benzenediamine (T691): Preclinical Studies of a Potential New Tracer of Regional Cerebral Perfusion

Stephan F. Taylor, Kirk A. Frey, Ronald M. Baldwin^*, Stephen M. Papadopoulos, Neil A. Petry, W. Leslie Rogers, Bill J. McBride, Janice M. Kerr and David E. Kuhl

Departments of Internal Medicine (Division of Nuclear Medicine), Psychiatry, and Neurosurgery, The University of Michigan, Ann Arbor, Michigan
Medi-Physics, Inc., Emeryville, California

Correspondence: For reprints contact: K. A. Frey, MD, PhD, The University of Michigan Hospitals, B1G 412/0028 AGH, 1500 E. Medical Center Dr., Ann Arbor, MI 48109.

ABSTRACT

We report in vitro and in vivo preclinical studies of a new cerebral blood flow tracer, [^99mTc]N1-(2-mercapto-2-methylpropyl)-N2-(2-propargylthio-2-methylpropyl)-1,2-benzenediamine (T691). The tracer demonstrates excellent in vitro chemical stability and accumulates regionally in the brain in a pattern consistent with that of cerebral blood flow. First-pass cerebral extraction determined with the use of the brain uptake index method in the rat was 0.76. Bolus intracarotid injection in monkeys indicated a cerebral extraction of 68% and prolonged retention of 67% of the initially extracted activity. Autoradiographic studies in rats revealed a pattern characteristic of cerebral blood flow at both 1 and 60 min after systemic injection. Dynamic tomographic imaging following systemic injection in the monkey revealed peak brain activity 1 to 2 min postinjection, without significant decline over 60 min. Chromatographic studies of brain as long as 60 min following systemic injection of [^99mTc]T691 showed no evidence of tracer metabolism to account for its retention. Overall, [^99mTc]T691 demonstrates promise as a potential new clinical tracer of cerebral perfusion.

FOOTNOTES

^* Current address: Yale University, VA Medical Canter, New Haven, CT.

Current address: Diatech Inc., Londonderry, NH.

Current address: Chiron Inc., Emeryville, CA.