title: Noninvasive monitoring of the fate of 111In-labeled block copolymer micelles by high resolution and high sensitivity microSPECT/CT imaging.
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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Hoang
authors.forename: Helen
authors.initials: H
authors.lastname: Lee
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Reilly
authors.forename: Christine
authors.initials: C
authors.lastname: Allen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002208:Caproates / Q000737:chemistry; D003952:Diagnostic Imaging; D004337:Drug Carriers; D005260:Female; D007205:Indium Radioisotopes; D007783:Lactones / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals; D013816:Thermodynamics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D001672:Biocompatible Materials; D002208:Caproates; D004337:Drug Carriers; D007205:Indium Radioisotopes; D007783:Lactones; D008823:Micelles; D011108:Polymers; D019275:Radiopharmaceuticals; C109600:indium benzyldiethylenetriaminepentaacetic acid; D011092:Polyethylene Glycols; C121056:caprolactone; D004369:Pentetic Acid