© Neuroscience-Net Volume 1, Article #00010

Received July 6, 1996 Accepted for Publication September 18, 1996 Published October 22, 1996

Alan J. Fischman¹, Ali. A. Bonab¹, John W. Babich¹, Nathaniel M. Alpert¹, David R. Elmaleh¹, Sandra A. Barrow¹, Wendy Graham^1, Peter Meltzer², Robert N. Hanson³, Bertha K. Madras⁴

¹Division of Nuclear Medicine of the Department of Radiology, Massachusetts General Hospital, and the Department of Radiology, Harvard Medical School, Boston MA. ²Organix Inc., Boston MA. ³Department of Chemistry, Northeastern University, Boston MA. ⁴Harvard Medical School, Boston MA and The New England Regional Primate Center, Southborough, MA.

Reprint requests should be addressed to:	Correspondence should be addressed to:
Dr. Alan J. Fischman Division of Nuclear Medicine Department of Radiology Massachusetts General Hospital 32 Fruit Street Boston, MA 02114 (617) 726-8353	Dr. Bertha K. Madras Division of Neurochemistry New England Regional Primate Research Ctr. Harvard Medical School 1 Pine Hill Drive Southborough, MA 01772-9102 email: bmadras@warren.med.harvard.edu

The cocaine analog 2b-carbomethoxy-3b-(4-fluorophenyl)-n-(1-iodoprop-1-en-3-yl) nortropane ([¹²³I] IACFT) labeled dopamine transporters in brain striatum. Preliminary single photon emission computed tomography (SPECT) studies with [¹²³I] IACFT were performed in two healthy volunteers. Serial SPECT images were acquired over 2 hrs. Arterial blood samples were collected in parallel with imaging, and plasma radioactivity was analyzed chromatographically to derive metabolite corrected arterial input functions. Binding potential (BP, B'_max / K_D) for striatal (Str) dopamine transporter (DAT) sites was measured by 2 methods using the occipital cortex (Occ) as reference. In the first method, the time-activity data was analyzed by the linear graphical method developed for reversible receptor ligands by Logan et al. For the second method, the expression (Str_TAC - Occ_TAC) was fitted to a gamma variate function and the maximum was used to estimate BP (Farde, et al.). Plasma analysis indicated that [¹²³I]-IACFT is rapidly converted to polar metabolites. The imaging results showed that [¹²³I]-IACFT accumulates rapidly and selectively in the striatum and yields excellent quality images within one hour after injection. DAT selectivity of [¹²³I]-IACFT was indicated by absence of tracer accumulation in 5-HT transporter rich regions of the hypothalamus and mid-brain. Binding potential measured by the 2 methods were remarkably similar; subject 1: method 1- 1.81, method 2-1.88, subject 2: method 1 - 3.00, method 2 - 3.04. These results demonstrate that [¹²³I]-IACFT is a promising SPECT ligand for imaging and quantification of DAT sites in the human brain.