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Mice bearing EMT-6 mammary carcinomas received a single intravenous injection of 1. 9 nm-diameter gold particles (AuroVist™-1. 9 nm), up to 2. 7 g Au/kg body weight, which elevated concentrations of gold to 7 mg [Au]/g in tumors. Tumor-to-normal-tissue gold concentration ratios remained ~8:1 during several minutes of 250 kVp X-ray therapy. Tumor volume was then monitored over 30 days in four groups of mice: (a) no treatment; (b) gold only (1.
Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Our research has focused on developing novel small molecules based PET probes targeting melanoma associated specific targets such as melanin, etc. Small molecule benzamide analogs can bind with melanin overproduced in malignant melanoma. Through rational design of the probes and further in vivo evaluation of several PET radionuclide labeled compounds, we have successfully identified 18F-benzamide analogs 18F-FBZA, 18F-P3BZA, 18F-FPDA which display excellent properties for melanoma imaging. Especially, 18F-P3BZA was found to specifically target melanoma with high tumor uptakes and good tumor to normal tissue.
Neurolemoma A benign, encapsulated neoplastic tissue consisting of Schwann cells. Oncogenes A family of genes that may foster malignant processes if mutated or activated by retrovirus. Ossification The formation of bone. Papilloma A benign epithelial neoplasm. Pedunculated A stalk-like connecting structure attaching a tumor to normal tissue.
, protoporphyrin IX (PpIX) was conjugated with cyclic RGDfK peptide (Fig. 19). It retained their respective photodynamic and integrin binding activity. The PpIX:cRGDfK conjugate is shown to be a good photosensitiser in vitro in the integrin positive human SiHa cell line and in vivo in a mouse CaNT tumor model. Moreover, pharmacokinetic analysis of PpIX:cRGDfK treated mice showed significant retention and accumulation of photosensitizer in tumor tissue with higher tumor : normal tissue.
The orthotopic gliomas beared mice was subcutaneous injected with AF680-labeled 1D11, a pan-neutralizing TGF-β antibody, and used for the bio-distribution study via in vivo imaging and fluorescence microscopy. With the combination of results from direct tumor size measurement, H&E staining and immune-histochemistry, it demonstrate that TGF-β plays different roles in combating the tumor depending on subcutaneous versus orthotopic implantation site . Besides the monoimaging principle, combining two or more different imaging modalities in the same agent can be of considerable value in molecular imaging. By binding a biotinylated anti-Her2 Herceptin antibody to provide tumor targeting, a biotinylated DOTA chelator labeled with 111In and a biotinylated Cy5. 5 fluorophore to a streptavidin nanoparticle, the imaging results show high tumor accumulation and strong tumor-to-normal tissue.
These novel affinity molecules possess valuable properties including small size, high affinity and specificity, high thermal stability, and straightforward generation. Moreover, since ADAPTs have the unique feature of binding to disease-related targets while retaining the affinity for serum albumin, the in vivo pharmacokinetic properties can be finely adapted for a given application. To demonstrate this and to further expand the utility of these proteins, we re-engineered a bispecific HER2-binding ADAPT by eradicating the albumin-binding to decrease the in vivo half life, which consequently made it suitable for molecular imaging. The engineered molecule, denoted ADAPT6, was investigated in HER2-positive xenograft models and demonstrated high, specific and HER2-dependent uptake in tumors together with high tumor-to-normal tissue.
In hypoxic cells, nitro-imidazole compounds are reduced by intracellular reductases into highly reactive intermediates, which subsequently bind to thiol groups of intracellular proteins, resulting in accumulation inside hypoxic cells (19). Multiple studies have been performed to improve in vivo stability of substrates with nitro-groups against enzymatic cleavage for visualization of tumor hypoxia using both SPECT (20) and PET (21). Among these hypoxia imaging agents are the fluoromisonidazole (18F-FMISO) (22) and the recently designed 18FHX4 with improved pharmacokinetic and clearance properties (23). A major challenge in development of nitro-imidazole-based imaging agents for hypoxia is the need to penetrate inside malignant cells, which requires sufficiently high lipophilicity of a tracer. A high lipophilicity slows down elimination of an unbound tracer from normal tissues, which reduces tumor to normal tissue.