Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

BACKGROUND: Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. METHODS: The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. RESULTS: Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. CONCLUSIONS: This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

Optical properties of human brain and tumour tissue: An ex vivo study spanning the visible range to beyond the second near-infrared window.

Neuro-oncology surgery would benefit from detailed intraoperative tissue characterization provided by noncontact, contrast-agent-free, noninvasive optical imaging methods. In-depth knowledge of target tissue optical properties across a wide-wavelength spectrum could inform the design of optical imaging and computational methods to enable robust tissue analysis during surgery. We adapted a dual-beam integrating sphere to analyse small tissue samples and investigated ex vivo optical properties of five types of human brain tumour (meningioma, pituitary adenoma, schwannoma, low- and high-grade glioma) and nine different types of healthy brain tissue across a wavelength spectrum of 400 to 1800 nm. Fresh and frozen tissue samples were analysed. All tissue types demonstrated similar absorption spectra, but the reduced scattering coefficients of tumours show visible differences in the obtained optical spectrum compared to those of surrounding normal tissue. These results underline the potential of optical imaging technologies for intraoperative tissue characterization.

Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment.

Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.

Multibranched Gold Nanoparticles with Intrinsic LAT-1 Targeting Capabilities for Selective Photothermal Therapy of Breast Cancer.

Because of the critical role of the large neutral amino acid transporter-1 (LAT-1) in promoting tumor growth and proliferation, it is fast emerging as a highly attractive biomarker for the imaging and treatment of human malignancies, including breast cancer. While multibranched gold nanoparticles (AuNPs) have emerged as a promising modality in the photothermal therapy (PTT) of cancers, some of the key challenges limiting their clinical translation lie in the need to develop reproducible and cost-effective synthetic methods as well as the selective accumulation of sufficient AuNPs at tumor sites. In this study, we report a simple and direct seed-mediated synthesis of monodispersed multibranched AuNPs using the catechol-containing LAT-1 ligands, L- and D-dopa, to confer active cancer targeting. This route obviates the need for additional conjugation with targeting moieties such as peptides or antibodies. Nanoflower-like AuNPs (AuNF) with diameters of approximately 46, 70, and 90 nm were obtained and were found to possess excellent colloidal stability and biocompatibility. A significantly higher intracellular accumulation of the L- and D-dopa functionalized AuNFs was observed in a panel of breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468, and MDA-MB-453) when compared to the nontargeting control AuNFs synthesized with dopamine and 4-ethylcatechol. Importantly, no significant difference in uptake between the targeting and nontargeting AuNFs was observed in a non-tumorigenic MCF-10A breast epithelial cell line, hence demonstrating tumor selectivity. For PTT of breast cancer, Ag+ was introduced during synthesis to obtain L-dopa functionalized nanourchin-like AuNPs (AuNUs) with strong near-infrared (NIR) absorbance. The L-dopa functionalized AuNUs mediated selective photothermal ablation of the triple negative MDA-MB-231 breast cancer cell line and sensitized the cells to the anticancer drugs cisplatin and docetaxel. This work brings forward an effective strategy for the facile preparation of cancer targeting multibranched AuNPs with potential for the in vivo PTT of breast cancer.

Change in the intrathyroidal kinetics of radioiodine under continued and discontinued antithyroid medication in Graves' disease.

PURPOSE: This study evaluated the thyroidal kinetics of radioiodine in Graves' disease under continued thiamazole medication and after discontinuation of thiamazole for 1-2 days, with a view to keeping the period of discontinuation as short as possible and to exploring the underlying mechanism of a postulated radioprotective effect of antithyroid drugs. METHODS: In 316 patients, diagnostic and therapeutic radioiodine kinetics were followed up for 2 days by ten uptake measurements each and were defined mathematically by a two-compartment model. RESULTS: Without thiamazole or when thiamazole was discontinued for at least 2 days, all uptake curves could be fitted perfectly by a simple in- and output function; the mean square error (mse) was 0.38 (test) and 0.28 (therapy). Under continued thiamazole medication (11.0+/-7.0 mg/day), the energy dose delivered to the thyroid was lowered by factor of 2.5. Uptake curves were deformed (mse: 1.06, test and 0.86, therapy) and appeared two peaked, suggesting coexistence of follicles with blocked and follicles with intact hormone synthesis and hence heterogeneous radioiodine uptake in the thyroid. In patients with maximally altered uptake curves, the success rate was as low as 31%. One day after discontinuation of thiamazole, mse was still increased (0.78, test), while 2 days afterwards it had normalised (0.36, test) and 3 days afterwards (mse: 0.24, therapy) the success rate was 87%. CONCLUSION: Efficacy of radioiodine therapy under continued thiamazole medication is reduced not only by a lower uptake and shorter half-life of radioiodine, but also by a heterogeneous energy dose distribution in the thyroid. Discontinuation of thiamazole (but probably not of propylthiouracil) for at least 2 days is required to restore the efficacy of radioiodine.