Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies.

Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody (mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, image-guided and spatiotemporally controlled elimination of tumor cells. Here, we report the highly efficient NIR-PIT of human tumor xenografts initiated from patient-derived cancer stem cells (CSCs). Using glioblastoma stem cells (GBM-SCs) expressing the prototypic CSC marker AC133/CD133, we also demonstrate here for the first time that NIR-PIT is highly effective against brain tumors. The intravenously injected theranostic AC133 mAb conjugate enabled the non-invasive detection of orthotopic gliomas by NIR fluorescence imaging, and reached AC133+ GBM-SCs at the invasive tumor front. AC133-targeted NIR-PIT induced the rapid cell death of AC133+ GBM-SCs and thereby strong shrinkage of both subcutaneous and invasively growing brain tumors. A single round of NIR-PIT extended the overall survival of mice with established orthotopic gliomas by more than a factor of two, even though the harmless NIR light was applied through the intact skull. Humanised versions of this theranostic agent may facilitate intraoperative imaging and histopathological evaluation of tumor borders and enable the highly specific and efficient eradication of CSCs.

Real-time MR temperature mapping of rabbit liver in vivo during thermal ablation.

It has been shown that quantitative MRI thermometry using the proton resonance frequency (PRF) method can be used to noninvasively monitor the evolution of tissue temperature, and to guide minimally-invasive tumor ablation based on local hyperthermia. Although hepatic tumors are among the main targets for thermal ablation, PRF-based temperature MRI of the liver is difficult to perform because of motion artifacts, fat content, and low T(*) (2). In this study the stability of real-time thermometry was tested on a clinical 1.5 T scanner for rabbit liver in vivo. The fast segmented EPI principle was used together with respiratory gating to limit respiratory motion artifacts. Lipid signal suppression was achieved with a binomial excitation pulse. Saturation slabs were applied to suppress artifacts due to flowing blood. The respiratory-gated MR thermometry in the rabbit liver in vivo showed a standard deviation (SD) of 1-3 degrees C with a temporal resolution of 3 s per slice and 1.4 mm x 1.9 mm spatial resolution in plane (slice thickness = 5 mm). The method was used to guide thermal ablation experiments with a clinical infrared laser. The estimated size of the necrotic area, based on the thermal dose calculated from MR temperature maps, corresponded well with the actual lesion size determined by histology and conventional MR images obtained 5 days posttreatment. These results show that quantitative MR temperature mapping can be obtained in the liver in vivo, and can be used for real-time control of thermal ablation and for lesion size prediction.