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Abstract #3947

Evaluation of a Cerebral-Blood-Volume (CBV) pharmaco-MRI (phMRI) Assay Utilizing Low (0.1mg/70kg) and High (0.2mg/70kg) Dose Buprenorphine Infusion and a Novel USPIO Contrast Agent (Ferumoxytol) in Healthy Human Subjects.

Richard Baumgartner 1 , Arie Struyk 2 , Jeff Evelhoch 2 , Cynthia Gargano 2 , Francheska Colon Gonzalez 2 , Haiying Liu 1 , Ruben Declercq 3 , Hans Verheyden 3 , Ingeborg Heirman 3 , Hans De Pla 4 , Griet Van Lancker 4 , Sofie Van den Abeele 4 , Adelheid Hollebosch 4 , Brant Delafontaine 4 , Luc Van Bortel 4 , Rik Achten 4 , Patricia Clement 4 , Pieter Vandemaele 4 , Dai Feng 1 , and Sofia Apreleva 1

1 Merck and Co, Rahway, New Jersey, United States, 2 Merck and Co, Pennsylvania, United States, 3 Merck and Co, Belgium, 4 Ghent University, Belgium

We present results from a clinical trial of pharmaco-MRI (phMRI) employing cerebral blood volume (CBV) imaging using ferumoxytol (Rienso/Feraheme, AMAG) as a blood pool contrast agent. The study examined the pharmacodynamic effects of two single doses of buprenorphine (0.2mg/70kg and 0.1mg/70kg administered intravenously). We found that contrast-enhanced CBV phMRI signals are more sensitive reporters of pharmacodynamic effects than conventional blood oxygen level dependent (BOLD) phMRI. In particular, higher sensitivity of CBV phMRI compared to BOLD allows for elucidation of PD responses at lower doses of buprenorphine, which has practical implications for similar phMRI studies with centrally acting drugs.

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