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  • Title: Noninvasive monitoring of the fate of 111In-labeled block copolymer micelles by high resolution and high sensitivity microSPECT/CT imaging.
    Author: Hoang B, Lee H, Reilly RM, Allen C.
    Journal: Mol Pharm; 2009; 6(2):581-92. PubMed ID: 19718806.
    Abstract:
    The validation of high sensitivity and high resolution microSPECT/CT imaging for tracking the in vivo pathway and fate of an 111Indium-labeled (111In) amphiphilic diblock copolymer micelle formulation is presented. Heterobifunctional poly(ethylene glycol) was used to initiate cationic ring opening polymerization of epsilon-caprolactone, which was then conjugated to 2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (p-SCN-Bn-DTPA) for chelation with 111In. The micelles were characterized in terms of their physicochemical properties including size, size distribution, zeta-potential, and radiochemical purity. Elimination kinetics and tissue deposition were evaluated in healthy mice following administration of 111In-micelles, 111In-DTPA-b-PCL unimers (i.e., administered under the critical micelle concentration) or 111In-Bn-DTPA. Healthy and MDA-MB-231 tumor-bearing mice were imaged using microSPECT/CT following iv administration of 111In-micelles or 111In-Bn-DTPA. Overall, incorporation of 111In onto the surface of thermodynamically stable micelles results in long plasma residence times for the radionuclide and preferential localization within the spleen (22 +/- 5% i.d/g), liver (13 +/- 3% i.d./g), and tumor (9 +/- 2% i.d./g). MicroSPECT/CT imaging provided noninvasive longitudinal visualization of circulation dynamics and tissue deposition. A strong correlation between image-based region of interest (ROI) analysis and biodistribution data was found, implying that nuclear imaging can be used as a noninvasive tool to accurately quantify tissue distribution. As well, the image-based assessment provided unique insight into the intratumoral distribution of the micelles in vivo.
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