Noninvasive positron emission tomography and fluorescence imaging of CD133 ⁺ tumor stem cells

TLDR

A technology that visualizes tumor stem cells with clinically relevant tracers could have a broad impact on cancer diagnosis and treatment, and the AC133 epitope of CD133 is one of the best‑characterized tumor stem cell markers for many intra‑ and extracranial tumor entities. The study aims to demonstrate noninvasive detection of AC133(+) tumor stem cells using PET and near‑infrared fluorescence imaging. It employs antibody‑based tracers, specifically (64)Cu‑NOTA‑AC133 mAb, in subcutaneous and orthotopic glioma xenografts. MicroPET with (64)Cu‑NOTA‑AC133 mAb produced high‑quality images with excellent tumor‑to‑background contrast, clearly delineating subcutaneous tumor stem cell–derived xenografts and detecting intracerebral tumors as small as 2–3 mm, thereby reflecting the invasive growth pattern of orthotopic cancer stem cell–derived tumors with low AC133(+) cell density and providing a basis for further preclinical and clinical use of these tracers.

Abstract

A technology that visualizes tumor stem cells with clinically relevant tracers could have a broad impact on cancer diagnosis and treatment. The AC133 epitope of CD133 currently is one of the best-characterized tumor stem cell markers for many intra- and extracranial tumor entities. Here we demonstrate the successful noninvasive detection of AC133(+) tumor stem cells by PET and near-infrared fluorescence molecular tomography in subcutaneous and orthotopic glioma xenografts using antibody-based tracers. Particularly, microPET with (64)Cu-NOTA-AC133 mAb yielded high-quality images with outstanding tumor-to-background contrast, clearly delineating subcutaneous tumor stem cell-derived xenografts from surrounding tissues. Intracerebral tumors as small as 2-3 mm also were clearly discernible, and the microPET images reflected the invasive growth pattern of orthotopic cancer stem cell-derived tumors with low density of AC133(+) cells. These data provide a basis for further preclinical and clinical use of the developed tracers for high-sensitivity and high-resolution monitoring of AC133(+) tumor stem cells.