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Synthesis and Biodistribution of Neutral Lipid-Soluble Tc-99m Complexes that Cross the Blood-Brain Barrier

SUNY at Buffalo and VA Medical Center, Buffalo, New York

Correspondence: For reprints contact: Hank F. Kung, PhD, Building 5, V.A. Med. Ctr., Buffalo, NY 14215.

ABSTRACT

Three Tc-99m-labeled neutral 1,2-dithla-5,8-diazacyclodecane (BAT) chelates that are capable of crossing the blood-brain barrier (BBB) were prepared and evaluated. Biodistribution (i.v.) in rats showed a significant brain uptake (1–3%/whole brain) at 2 min. At 15 min the uptake dropped to about a tenth of the original level, indicating free passage in both directions across the BBB. Gamma camera images of a monkey confirmed the high initial brain uptake. This group of Tc-99m BAT compounds clearly exhibited in vivo stability and the ability to cross the BBB after an i.v. injection. Derivatives containing tertiary amine groups should have prolonged brain retention and might be suitable for SPECT studies of brain perfusion.

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