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The synthesis and properties of a bimetallic complex containing a luminescent rhenium chromophore as well as a [Gd.sup.3+] ion that is used in magnetic resonance imaging (MRI) are described. The luminescence lifetimes are long enough for permitting efficient gating of any fluorescent background, while the gadolinium ion is used for providing magnetic resonance (MR) contrast.

Fluorescein- and terbium-labelled tuftsin (Thr-Lys-Pro-Arg) and pentapeptide (Thr-Lys-Pro-Pro-Arg) were synthesized and their properties were evaluated in vitro by luminescence spectrometry and confocal microscopy as fluorescence probes to target macrophage cells in biological systems. An increase in fluorescence of macrophages incubated with varying concentrations of fluorescein isothiocyanate or Tb-DOTA-tuftsin/pentapeptide conjugates was observed in a concentration-dependent manner. Tb-DOTA-pentapeptide had a greater affinity to macrophages than Tb-DOTA-tuftsin. Lipopolysaccharide (LPS) stimulation strengthened the internalization of peptide conjugates by macrophages through the tuftsin receptor mechanism. Tb-DOTA-tuftsin/pentapeptide conjugates are likely to be a promising optical reagents as probes of the immune response with involvement of macrophage cells in a variety of diseases. Gd-DOTA-tuftsin conjugate was also evaluated as a cell-specific contrast agent in in vitro MRI experiments. In this context, the macrophages labelled by Gd-DOTA-tuftsin were highly magnetic and detectable by MRI, which confirms that this vectorized MRI probe has the potential to image macrophage-mediated inflammation in diseases like brain traumas and stroke. Tuftsin receptor-specific biological-function domain may have a modified in vivo biodistribution profile, bioavailability and pharmacokinetics subsequent to its conjugation to a metal ion-binding backbone. Copyright © 2010 John Wiley & Sons, Ltd. Tb-DOTA-tuftsin/pentapeptide and Gd-DOTA-tuftsin conjugates were evaluated as promising optical reagents and as a cell-specific MRI contrast agent to probe the immune response with involvement of macrophage, respectively. Tuftsin receptor-specific biological-function domain may have a modified in vivo biodistribution profile, bioavailability and pharmacokinetics. [ABSTRACT FROM AUTHOR]

We studied antiangiogenic and antilymphangiogenic effects of sVEGFR-1 (sFlt-1), sVEGFR-2 (sFlk-1/KDR), and sVEGFR-3 (sFlt-4) gene transfers and their combinations in intraperitoneal ovarian cancer xenograft mice (Balb/c-Anu, n = 55). Gene therapy was initiated when the presence of sizable tumors was confirmed in magnetic resonance imaging (MRI). Adenovirus-mediated gene transfer was performed intravenously via tail vein as follows: AdLacZ as a control (group I), AdsFlt-1 (group II), AdsKDR (group III), AdsFlt-4 (group IV) and two combination groups of AdsFlt-1 and AdsFlt-4 (group V) and AdsFlt-1, AdsKDR, and AdsFlt-4 (group VI). Antitumor effectiveness was assessed by sequential MRI, immunohistochemistry, microvessel density, overall tumor growth, and survival time. In combination group VI, intraperitoneal tumors were significantly smaller than in the control group at the end of the follow-up (P < 0.001). Furthermore, in group VI the microvessel density (microvessels/mm2) in tumor tissue and the total area of tumors covered by microvessels were significantly smaller than in the controls. One mouse in group V was cured. The combined antiangiogenic gene therapy with soluble VEGFRs reduced tumor growth, tumor vascularity, and ascites formation in ovarian cancer xenografts. The results suggest that the combined antiangiogenic gene therapy is a potential approach for the treatment of ovarian cancer patients.Molecular Therapy (2009) 17 2, 278–284 doi:10.1038/mt.2008.258 [ABSTRACT FROM AUTHOR]

Abstract: Objective.: Typically, human ovarian cancer is widely disseminated at the time of diagnosis and shows extremely poor prognosis. Experimental animal models that mimic human ovarian cancer are often incomplete when compared to the full spectrum of the human disease with regard to its histological hallmarks such as the spread of carcinoma, its ability to seed the peritoneal cavity and formation of ascites. We have established and characterized a new animal model for human ovarian cancer in nude mouse. Methods.: A new cell line SKOV-3m was injected intraperitoneally in nude mice. Mice were divided in two groups A and B, which received 1×107 and 2×107 cells, respectively. Histology, immunohistochemistry, magnetic resonance imaging and ultrasound were used to analyze tumors. Results.: All mice had tumors within 18 days and histologically they resembled poorly differentiated human cystadenocarcinomas with bloody ascites. Mean survival of the mice was 42±14 and 21±2 days in groups A and B, respectively. Magnetic resonance imaging and ultrasound were used to confirm the presence of tumors and to monitor their growth without sacrificing the animals. Conclusion.: This new xenograft model accompanied by noninvasive imaging is highly reproducible and likely to be very useful in testing new treatment strategies for ovarian cancer. [Copyright &y& Elsevier]