Synthesis and comparison of 99mTc-enrofloxacin and 99mTc-ciprofloxacin.
The use of (99m)Tc-ciprofloxacin as a tracer for infection and inflammation has been examined and discussed in the literature extensively. Its alleged ability to discriminate between sterile inflammation and bacterial versus nonbacterial infections has led to an intense debate. Other labeled fluoroquinolones might offer better characteristics or may add to a better understanding of the working mechanism of (99m)Tc-ciprofloxacin. The rationale of this work was to determine possible differences in the use of 2 labeled quinolones--that is, (99m)Tc-ciprofloxacin and (99m)Tc-enrofloxacin--as tracers for infection and inflammation in animals.


METHODS
Ciprofloxacin and enrofloxacin were labeled with (99m)Tc and characterized. The stability of both preparations was evaluated in serum and in the presence of an excess of cysteine. In vitro binding studies were performed to determine the interaction of the labeled quinolones with bacteria and other cells. Rats with sterile and infectious intramuscular lesions were used to study the scintigraphic properties of the 2 compounds. To assess the specificity of binding to living bacteria, infectious intramuscular lesions of heat-killed Staphylococcus aureus and Candida albicans were used as controls. Imaging was performed with a gamma-camera at 0, 3, 5, and 22 h after injection.


RESULTS
The radiochemical purity of both radiolabeled fluoroquinolones exceeded 95% as determined by instant thin-layer chromatography. Both compounds were moderately stable in serum. Binding assays did not show any saturable binding to S. aureus, heat-killed S. aureus, as well as C. albicans. None of the tracers showed specific binding to bacteria. Scintigraphy showed uptake in the infectious lesion at 1 h after injection, which washed out during the next 4 h. Abscess-to-muscle ratios for both preparations were not significantly different for the various infectious or inflammatory lesions studied and did not exceed an average of 4.25 +/- 0.62.


CONCLUSIONS
The study demonstrated that (99m)Tc-ciprofloxacin and (99m)Tc-enrofloxacin do not show preferential binding to living bacteria. In vivo (99m)Tc-enrofloxacin has similar characteristics as (99m)Tc-ciprofloxacin except for differences in uptake in a few normal tissues.
Siaens
Rien H
RH
Laboratory of Radiopharmacy, Gent University, 9000 Gent, Belgium. Rien.Siaens@ugent.be
Rennen
Huub J
HJ
Boerman
Otto C
OC
Dierckx
Rudi
R
Slegers
Guido
G
D000818:Animals; D002176:Candida albicans / Q000378:metabolism; D002177:Candidiasis / Q000000981:diagnostic imaging* / Q000378:metabolism; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015363:Quinolones / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism; D013667:Technetium / Q000493:pharmacokinetics; D013848:Thigh / Q000382:microbiology
D024841:Fluoroquinolones; D015609:Organotechnetium Compounds; D015363:Quinolones; C431804:Technetium Tc 99m ciprofloxacin; D000077422:Enrofloxacin; D002939:Ciprofloxacin; D013667:Technetium