Monitoring cholesterol transport in vivo by PET

Objectives Incidences of diseases characterized by alterations in cholesterol homeostasis (e.g., atherosclerosis, obesity, diabetes) are increasing. Thus, there is a growing need for methods for comprehensive quantitative evaluation of such alterations. The data reported previously are not sufficiently detailed due to the limited capabilities of early imaging modalities. In a present study, we took advantage of the superior spatial and time resolution of PET to develop an imaging method for quantitative real-time monitoring of the transport of cholesterol in vivo.

Methods 19-Iodocholesterol (IC) was synthetized following the published procedures and radiolabeled with ¹²⁴I by isotope exchange with the radiochemical yield and purities of 58% and 75%, respectively. Biokinetics of [¹²⁴I] was studied by PET in six SD rats (~250 g). To this end, [¹²⁴I]IC was incorporated in the lipidic component of the rat plasma and administered IV. Dynamic and static images were acquired for 4 days using microPET Focus 220 imager (Siemens) interfaced with CereTom NL 3000 CT scanner (Neurologica). Time dependences of organ uptake were quantified by ROI analysis.

Results Initial de-halogenation and labile ¹²⁴I content did not exceed 5% of the injected dose (%ID) as quantified by total [¹²⁴I]IC accumulation in the thyroid, bladder, and stomach walls. Liver was the organ of the greatest uptake over the entire period of observation. Other, minor sites of [¹²⁴I]IC uptake included: kidneys, spleen, pancreas, large and small intestines, caecum, lungs, muscle, and fat. Progressive accumulation of [¹²⁴I]IC in the adrenal gland at up to 0.7%ID has been characteristic and was consistent with the reported behavior of cholesterol in vivo.

Conclusions [¹²⁴I]IC is a stable probe suitable for long-term imaging of cholesterol transport in vivo by PET and quantification of the kinetic manifestations of the alterations in cholesterol homeostasis.

Research Support NIH