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Abstract: Purpose: The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors, and its role in adipogenesis and glucose metabolism has been well established. PPAR-γ agonists have been shown to inhibit many cytokines and to have anti-inflammatory effects. In pathologic conditions, enhanced fluoro-2-deoxy-d-glucose (FDG) uptake is observed not only in malignant tumors but also in inflammatory lesions, and this uptake occurs through the glucose transporter in these cells. Thus, the present study was undertaken to investigate the potential of using PPAR-γ''s glucose uptake ability as a diagnostic tool to differentiate between macrophage and tumor cells. Materials and Methods: Cellular uptake studies were carried out on macrophage and two tumor cell lines for comparison by using 18F-FDG. Western blot analysis was performed to determine the expression levels of both the glucose transporter and hexokinase protein. To confirm the possibility of differentiation between tumor and inflammatory lesions using rosiglitazone based on in vitro studies, 18F-FDG (3.7×106 Bq) uptake in A549 and RAW 264.7 xenograft mice was compared. Results: The cellular uptake study findings were quite different for macrophages and tumor cells. 18F-FDG uptakes by macrophages decreased by about 60% but was increased twofold in tumor cells after rosiglitazone treatment. Moreover, the expressions of proteins related to glucose uptake correlated well with cellular glucose accumulation in both cell types. Higher tumor uptake was observed after the injection of rosiglitazone in A549 xenograft mice (1.58±0.55 to 4.66±1.16), but no significant change of 18F-FDG uptake was shown in RAW 264.7 xenograft mice (4.04±1.16 to 4.00±0.14). Conclusion: The present study demonstrates the roles of PPAR-γ agonist on FDG uptake in macrophages and tumor cells in vitro and in vivo. Our findings suggest that rosiglitazone has the potential to increase the contrast between tumor and inflammatory lesions. [Copyright &y& Elsevier]

Syntheses and evaluation of fluoroalkylated ciprofloxacin analogues are described. Among these analogues, N₄'-3-fluoropropylciprofloxacin (16) showed the most efficient antibacterial activity against E. coli strains (DH5α and TOP10) and a high binding affinity for DNA gyrase of bacteria. To develop bacteria-specific infection imaging agents for positron emission tomography (PET), no-carrier-added N₄-3-[¹⁸F]fluoropropylciprofloxacin ([¹⁸F]16) was prepared in two steps from N₄-3-methanesufonyloxypropylciprofloxacin, resulting in a 40% radiochemical yield (decay corrected for 100 min) via the tert-alcohol media radiofluorination protocol with high radiochemical purity (> 99%) as well as high specific activity (149 ± 75 GBq/μmol). The agent was stable (> 90%), as shown by an in vitro human serum stability assay. A bacterial uptake and blocking study of [¹⁸F]16 using authentic compound 16 in TOP10 cells demonstrated its high specific bacterial uptake. The results suggest that this radiotracer holds promise as a useful bacterial infection radiopharmaceutical for PET imaging.

The aim of this study was to investigate the effect of gluconic acid (GA) conjugation on the biodistribution of cysteamine-capped quantum dots (amino-QDots) in vivo. Cadmium selenide/zinc sulfide (CdSe/ZnS) was capped with cysteamine through a thiol exchange method, and different amounts of GA were conjugated to the amine groups of cysteamine via the formation of an amide bond. The emission maxima of the synthesized QDots, the amino-QDots and the GA-conjugated amine-QDots (GA-QDots) were located at 720, 600 and 610 nm, respectively. In the cell viability studies, the GA-QDots showed very low toxicity against CHO cells as compared to the cytotoxicity of the amino-QDots. The QDots were next intravenously injected into normal mice and then we performed ex vivo optical imaging. The majority of the amino-QDots were accumulated in the lung. In contrast, the GA-QDots were cleared out of the body through the kidney. Therefore, we expect that the conjugation of GA onto the amino-QDots can create opportunities for using amino-QDots for in vivo imaging.

Expression of vascular endothelial growth factor receptors (VEGFRs) increases in ischemic muscles, and thus, VEGFR could potentially be used as marker to detect ischemia. Here, we investigated whether (99m)Tc or Cy5.5-labeled chitosan-DC101 conjugates could identify VEGFR-2 overexpressed in ischemia. To this end, chitosan was conjugated with the DC101 antibody and Cy5.5, FITC, or the HYNIC chelator for (99m)Tc-labeling. Targeting of the conjugate was evaluated in vitro and in vivo through cell-binding studies and gamma/optical imaging, respectively. A hindlimb ischemic mouse model was surgically created by femoral artery occlusion. The chitosan-DC101 conjugates exhibited VEGFR-selective cell binding properties as determined by both confocal microscopy and flow cytometry. At postoperative times of 2, 12, and 24 h, (99m)Tc or Cy5.5-labeled chitosan-DC101 conjugates were intravenously injected into the mice, and gamma/optical imaging studies were conducted at 1 or 3 h. Both the gamma and optical imaging results indicated a significantly higher uptake in ischemic muscles when compared with the contralateral nonischemic muscle. Further, semiquantitative analysis of scintigraphic imaging data revealed that the ischemic to contralateral limb ratio was 4.5 +/- 0.25 at 24 h postoperation. Western blotting analysis confirmed VEGFR expression in the ischemic muscle. In conclusion, we believe that (99m)Tc or Cy5.5-labeled chitosan-DC101 conjugates have the potential to be useful as VEGFR-2-targeted imaging agents for monitoring ischemia., ((c) 2009 Wiley Periodicals, Inc.)

Mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase that has been shown to be overexpressed and mutated in a variety of malignancies, such as glioma. We have recently found that an (125)I-radiolabeled Gly-Gly-Gly (GGG)- or 8-aminooctanoic acid (AOC)-containing c-Met binding peptide (cMBP) specifically targets c-Met receptor in vivo and in vitro. In this report, cyanine dye 5.5 (Cy5.5)-conjugated GGG- or AOC-containing cMBPs were evaluated in human cancer cell xenografts in order to investigate the possibility of c-Met receptor targeting using an optical imaging system. The receptor binding affinity of Cy5.5-conjugated peptides was tested in 96-well plates coated with a c-Met/Fc chimeric protein. Optical imaging studies were performed in U87MG and Ramos bearing athymic mice. The binding affinities of Cy5.5-conjugated GGG- or AOC-containing cMBPs were determined to be 0.318 and 0.342 microM, respectively. Confocal images show that Cy5.5-conjugated peptides bound mainly to the cell surface and that peptide binding was clearly inhibited by free cMBP. Subcutaneous U87MG tumors were clearly visualized with each of the two fluorescent probes. Of the two, cMBP-AOC-Cy5.5 displayed higher tumor uptake and tumor-to-normal tissue ratios at 10 min to 24 h postinjection in the U87MG tumor model. For the in vivo blocking study, cMBP-AOC-Cy5.5 (4 nmol) was co-injected with cold cMBP (0.13 micromol) into the U87MG xenograft mice. Image-based tumoral uptake decreased up to approximately 35%. These results suggest that Cy5.5-conjugated cMBP could potentially be used to detect c-Met-positive cancers in vivo. However, additional modifications to this optical imaging agent are needed to further improve its efficacy.