Polymeric Micelle of A₃B-Type Lactosome as a Vehicle for Targeting Meningeal Dissemination

Abstract

Polymeric micelle of the A₃B-type lactosome comprising (poly(sarcosine))₃-b-poly(l-lactic acid) was labeled with ¹¹¹In. The ¹¹¹In-labeled A₃B-type lactosome was administered to the model mice bearing meningeal dissemination and bone metastasis at mandible. With single-photon emission computed tomography (SPECT) imaging, the meningeal dissemination was identified successfully by ¹¹¹In-labeled A₃B-type lactosome, which was superior to ²⁰¹TlCl in regard of the imaging contrast. The ¹¹¹In-labeled A₃B-type lactosome was also potential in imaging selectively of bone metastasis at mandible, whilst a nonspecific imaging of the whole bone was obtained by the SPECT imaging using ^99mTc-HMDP. The polymeric micelle of the A₃B-type lactosome was therefore found to be effective as a vehicle of ¹¹¹In to be targeted to meningeal dissemination and bone metastasis.

Keywords: SPECT; bone metastasis; meningeal dissemination; molecular imaging; polymeric micelle.

Figure 1

Schematic illustration of the labelling method of ¹¹¹In to DOTA-lactosome and the structure of ¹¹¹In-lactosome.

Figure 2

Luminescence and single-photon emission computed tomography (SPECT)/CT images of the B16F10 implanted mice. (A) Luminescence images for ventral and dorsal side of the mouse at 11 days after implantation; (B) Luminescence images for isolated brain of the mouse at 14 days after implantation; (C) Luminescence and photo images for brain cross-section isolated from the B16F10 implanted mouse at 14 days after cell injection; (D) SPECT/CT images using ¹¹¹In-lactosome for isolated brains of the mice at 14 days after implantation.

Figure 3

Dual isotope SPECT/CT images of melanoma metastasis mice after injections of ¹¹¹In-lactosome and ²⁰¹TlCl (A); and ¹¹¹In-Llctosome and ^99mTc-HMDP (B). The transverse (left), sagittal (middle), and coronal (right) views centered on the cerebral ventricle are shown.

Figure 4

Brain accumulation of ¹¹¹In-lactosome (¹¹¹In) and ²⁰¹TlCl (²⁰¹Tl) for intact and B16F10 metastasis mice (* p < 0.05). The sample number (n) = 10.