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Kinetic and metabolic considerations in the use of (I-125) HIPDM as a tracer for quantitative measurement of regional cerebral blood flow

Conference · · J. Nucl. Med.; (United States)
OSTI ID:6594212
The kinetics of cerebral uptake and the metabolism of radioactive iodine labeled HIPDM (N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-(I-125)iodobenzyl) -1,3-propanediamine)(I-125)HIPDM were studied in vivo in male adult Sprague-Dawley rats in order to evaluate the potential usefulness of this compound for quantitative measurement of regional cerebral blood flow (rCBF). The first pass extraction fraction of (I-125)HIPDM in brain was found to be about 80%. The arterial concentration of unmetabolized (I-125)HIPDM following an i.v. pulse drops rapidly and represents only 30% of the blood sample total radioactivity at 60 minutes, whereas 92% of the radioactivity in brain tissue at the same time is in unaltered (I-125)HIPDM. The rate constant for (I-125)HIPDM transport across the blood-brain barrier (BBB) was calculated on the basis of a distribution model in which bi-directional exchange of the tracer between brain tissue and vascular space is assumed. A kinetic model and an operational equation have been derived for determination of rCBF with this molecule. The model and equation take into account the three following factors: (a) incomplete first pass extraction; (b) HIPDM metabolism; (c) bi-directional flux of tracer across the BBB. The observations suggest that this molecule might be of potential usefulness for rCBF measurements with single photon emission tomography, provided that all these factors are evaluated in man.
Research Organization:
Lab. of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD
OSTI ID:
6594212
Report Number(s):
CONF-840619-
Conference Information:
Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
Country of Publication:
United States
Language:
English

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