hydrazino-nicotinamide and Abscess

It was previously shown that the (99m)Tc-labeled hydrazinonicotinamide (HYNIC)-conjugated LTB4 antagonist MB81 visualized infectious foci in rabbits adequately and within a few hours after injection. Here, the bivalent HYNIC-conjugated LTB4 antagonist MB67 (analog of MB81) was fluorinated with (18)F via hydrazone formation and tested in vivo.. MB67 was [(18)F]-fluorinated via reaction of the [(18)F]-fluorinated intermediate p-[(18)F]-fluorobenzaldehyde ([(18)F]FB) and the HYNIC moiety of MB67 via hydrazone formation. For comparison, MB67 was also labeled with (99m)Tc. The biodistribution of (18)F- and (99m)Tc-labeled MB67 was investigated in rabbits with intramuscular infection.. [(18)F]-MB67 was obtained at a maximum specific activity of 1200 GBq/mmol and proved to be stable in phosphate buffered saline (PBS) at 37 degrees C for at least 4 h. PET images obtained with [(18)F]-MB67 clearly delineated the abscess at 2 and 4 h pi. Counting of dissected tissues at 4 h pi revealed an abscess uptake of 0.073+/-0.005 %ID/g, as compared to 0.160+/-0.010 %ID/g for the (99m)Tc-labeled analog. Abscess-to-muscle ratios were 23+/-4 for [(18)F]-MB67 and 35+/-9 for [(99m)Tc]-MB67.. The present study showed the feasibility of a new [(18)F]-labeling methodology and its application in the production of a new PET tracer for imaging of infection, [(18)F]-MB67.

Topics: Abscess; Animals; Escherichia coli Infections; Fluorine Radioisotopes; Hydrazines; Hydrazones; Indicators and Reagents; Infections; Isotope Labeling; Leukotriene B4; Muscular Diseases; Niacinamide; Positron-Emission Tomography; Rabbits; Radiopharmaceuticals; Technetium; Tissue Distribution

In this study a new 99mTc labeling method for polyethyleneglycol (PEG)-coated liposomes is described. The in vitro and in vivo characteristics were compared with the conventional 99mTc-HMPAO-labeled PEG-coated liposomes.. PEG-coated liposomes were labeled with 99mTc by the hydrazino nicotinyl (HYNIC) derivative of distearoylphosphatidyl-ethanolamine (DSPE) and compared with PEG-coated liposomes labeled with 99mTc-HMPAO. In vitro stability tests were performed. Biodistribution and imaging characteristics of both liposomal preparations were determined in rats with Staphylococcus aureus infection in the left calf muscle.. Per liposome, 230 hydrazine groups were incorporated. The labeling efficiency of the 99mTc-HYNIC liposomes was greater than 95%, so no postlabeling purification was required, in contrast to the 99mTc-HMPAO liposomes. The 99mTc-HYNIC liposomes showed greater in vitro stability than the conventional 99mTc-HMPAO liposomes. Abscess uptake of the 99mTc-HYNIC liposomes was significantly greater (1.74+/-0.38%ID/g versus 1.26+/-0.29%ID/g, 24 h postinjection, P < 0.03). Furthermore, kidney uptake of the 99mTc-HYNIC liposomes was one third of the uptake of the 99mTc-HMPAO liposomes (0.79+/-0.07%ID/g versus 2.47+/-0.35%ID/g, 24 h postinjection, P < 0.0001).. This new 99mTc-HYNIC-based labeling method for liposomes is rapid, efficient and easy to perform. Most importantly, the 99mTc-labeled liposomes have an improved stability and in vivo characteristics. The new labeling method is a major step forward toward a radiopharmaceutical for infection imaging that can be prepared in a one-step procedure within 15 min at room temperature and thus can be applied in every routine clinical practice.

Topics: Abscess; Animals; Drug Carriers; Gamma Cameras; Hindlimb; Hydrazines; Liposomes; Male; Niacinamide; Phosphatidylethanolamines; Polyethylene Glycols; Radionuclide Imaging; Rats; Rats, Wistar; Staphylococcal Infections; Technetium; Technetium Tc 99m Exametazime; Tissue Distribution