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Molecular targeting of Alzheimer's amyloid plaques for contrast‐enhanced magnetic resonance imaging
Author(s) -
Poduslo J. F.,
Wengenack T. M.,
Curran G. L.,
Wisniewski T.,
Sigurdsson E. M.,
Macura S. I.,
Borowski B. J.,
Jack C. R.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.20_5.x
Subject(s) - magnetic resonance imaging , gadolinium , alzheimer's disease , molecular imaging , pathology , in vivo , amyloid (mycology) , chemistry , medicine , neuroscience , disease , biology , radiology , microbiology and biotechnology , organic chemistry
Smart molecular probes for both diagnostic and therapeutic purposes are expected to provide quantum advances in clinical medicine and biomedical research. We describe such a probe that targets amyloid plaques of Alzheimer's disease and has been labelled with gadolinium to impart contrast detectable by magnetic resonance imaging. Although amyloid plaques are a primary pathologic feature of Alzheimer's disease and amyloid reduction is a major therapeutic objective in Alzheimer's disease, no method currently exists for directly imaging human amyloid plaques in vivo . However, with the aid of a target specific contrast agent, imaging of amyloid plaques is theoretically possible with magnetic resonance imaging. We describe experiments proving that three essential properties exist in the smart molecular probe, putrescine‐gadolinium‐AB peptide: (1) transport across the blood–brain barrier following intravenous injection conferred by the polyamine moiety (2) binding to plaques with high affinity by putrescine‐AB, and (3) magnetic resonance imaging contrast by gadolinium. The plaque‐to‐background tissue contrast‐to‐noise ratio was enhanced more than 9 fold in all regions of cortex and hippocampus following intravenous administration of putrescine‐gadolinium‐AB in Alzheimer's disease transgenic mice. The ability of this magnetic resonance contrast probe to image plaques in vivo may enable early diagnosis and also provide a direct measure of the efficacy of antiamyloid therapies currently being developed. With the appropriate target specific probe (e.g. antibody), this technique could be applied to many other central nervous system disorders and targets.