RT Journal Article
SR Electronic
T1 Synthesis and evaluation of novel PET probes for P-gp expression and function
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 619
OP 619
VO 50
IS supplement 2
A1 van Waarde, Aren
A1 Ramakrishnan, Nisha
A1 Elsinga, Philip
A1 Berardi, Francesco
A1 Willemsen, Antoon
A1 Perrone, Roberto
A1 Cantore, Mariangela
A1 Dierckx, Rudi
A1 Colabufo, Nicola
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/619.abstract
AB 619 Objectives P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the brain against toxic substances. We labeled a modulator (MC266) and inhibitor (MC18) of the pump with 11C, resulting in potential tracers of P-gp function and expression. Methods MC18, MC266 and verapamil were labeled using 11CH3I. MicroPET scans (with arterial sampling) and biodistribution studies were performed in rats pretreated with saline, cyclosporin A (CsA), or cold MC18. Results Cerebral distribution volumes (DV) of 11C-MC18 (2.4±0.2) and 11C-MC266 (2.0±0.2) in untreated rats were higher than of 11C-verapamil (0.66±0.11). DVs of 11C-MC266 and 11C-verapamil were significantly increased by 50 mg/kg CsA (to 5.2±0.3 and 5.6±0.3, respectively). The DV of 11C-MC18 was reduced by cold MC18 (to 1.7±0.1). Its SUV was also reduced (up to 67%) in several peripheral organs which express P-gp. Conclusions 11C-MC266 is a novel tracer of Pgp function with higher baseline uptake than 11C-verapamil. Upregulation of P-gp function in response to treatment may be detectable using 11C-MC266 and PET. Since 11C-MC18 shows specific binding in target organs, this compound is a unique tracer of P-gp expression, although a derivative with higher affinity for the pump may be required for quantitative imaging. The prospect of independent assessment of pump function and expression is quite exciting.