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Extended Studies of the Striatal Uptake of ^99mTc-NC100697 in Healthy Volunteers

¹ Department of Nuclear Medicine, University of Munich, Munich, Germany; ² Department of Psychiatry, University of Munich, Munich, Germany; ³ Department of Neurology, University of Munich, Munich, Germany; ⁴ Department of Neuroradiology, University of Munich, Munich, Germany; and ⁵ GE Healthcare, Amersham, United Kingdom

Correspondence: For correspondence or reprints contact: Walter Koch, MD, Department of Nuclear Medicine, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. E-mail: walter.koch{at}med.uni-muenchen.de

This study evaluates a new formulation of a ^99mTc-labeled tropane derivate, ^99mTc-NC100697, in a human volunteer study. Methods: Eighty healthy subjects (39 females, 41 males) underwent MRI and SPECT (injected dose [mean ± SD], 10.6 ± 1.4 MBq/kg). Forty subjects were investigated 30, 90, 180, 240, 360, and 480 min after injection, and another 40 subjects were imaged 240 min after injection. Specific striatal binding was assessed using 3 different approaches: 3-dimensional volumes of interest (VOIs) drawn on the coregistered MRI scans, manually placed predefined 2-dimensional regions of interest (ROIs), and observer-independent fully automated 3-dimensional VOI analyses based on coregistration of scans with a mean template of controls. Specific striatal dopamine transporter (DAT) binding was estimated for cohorts of ages of 21–30, 31–40, 41–50, 51–60, 61–70, and 71–80 y. The relationship between age and DAT binding was analyzed with linear, "broken-stick," exponential, and logarithmic regression. Results: Serial SPECT scans revealed increasing values of specific DAT binding over time. Consideration of all important variables suggests an optimum imaging time at 4 h after injection. Average DAT binding for the total population was 1.1 ± 0.2 (striatum), 1.3 ± 0.2 (caudate), and 1.1 ± 0.2 (putamen), with mean putamen-to-caudate ratios of 0.83 ± 0.08 (manual 2-dimensional ROI method). A significant age dependency of striatal DAT binding, best described by a broken-stick (break-point age, 48 y) or logarithmic regression (both r = 0.76), with a lower decline observed in older than in younger subjects. Female subjects presented with slightly higher binding ratios than male subjects, more pronounced in pre- than in postmenopausal women. There was a high correlation between the 3 semiquantitative evaluations. Conclusion: The current study has demonstrated the effective use of ^99mTc-NC100697 for estimating presynaptic striatal DAT binding. The comparison of different semiquantification methods showed that in clinical routine work, this tracer can be reliably evaluated without individual MRI data. Age and a slight sex dependency (especially in premenopausal women) of ^99mTc-NC100697 binding should be taken into consideration. The data generated in this phase 1 study provides a basis for an age- and sex-matched normal database.

Key Words: quantitative evaluation • automated data processing • dopamine transporter

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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JNM 2007 48: 11a-12a. [Full Text]