PET imaging of infection with a HYNIC-conjugated LTB4 antagonist labeled with F-18 via hydrazone formation.
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.


METHODS
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.


RESULTS
[(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.


CONCLUSIONS
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.
Rennen
Huub J J M
HJ
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. h.rennen@nucmed.umcn.nl
Laverman
Peter
P
van Eerd
Julliëtte E M
JE
Oyen
Wim J G
WJ
Corstens
Frans H M
FH
Boerman
Otto C
OC
D000038:Abscess / Q000000981:diagnostic imaging; D000818:Animals; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006834:Hydrazines; D006835:Hydrazones / Q000138:chemical synthesis; D007202:Indicators and Reagents; D007239:Infections / Q000000981:diagnostic imaging*; D007553:Isotope Labeling; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D009135:Muscular Diseases / Q000000981:diagnostic imaging; D009536:Niacinamide / Q000031:analogs & derivatives*; D049268:Positron-Emission Tomography; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D006834:Hydrazines; D006835:Hydrazones; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; C117288:hydrazino nicotinamide; D007975:Leukotriene B4; D009536:Niacinamide; D013667:Technetium