RESUMO
UNLABELLED: This study aimed to investigate the biodistribution of the 99mTc-ceftizoxime in normal rats and in rats bearing septic and sterile induced abscess. MATERIAL AND METHODS: Three groups of rats were studied. a) Six normal rats b) 15 rats with E. coli induced abscess and c) 15 rats with sterile zymosan induced abscess. Septic abscess was induced with 2 x 10(8) colony forming units of E. coli and sterile one with 0.1 mL of 5% sterile Zymosan. 24 h after the abscess induction, 12 MBq of 99mTc-CFT were injected iv. and whole body images were collected at 30 min, 1, 2, 4 and 6 h p.i. Areas of interest were drawn and lesion/background index was calculated. The 6 normal rats were scanned at the same times, killed at 6 h p.i and kidney, liver, spleen, lung, heart and muscle activity were measured. Each organ was weighed, cut and its activity measured. Parallelly, the biological activity of the labeled antibiotic and its binding to the E. coli and S. aureus bacteria were analyzed. RESULTS: High biliary excretion was seen in all rats. Organ measurement showed the maximal uptake in kidney and very low uptake in muscles. Mean +/- s.d abscess/background ratio at 30 min, 1, 2, 4 and 6 h were 2.60 +/- 0.36, 2.67 +/- 0.66, 2.6 0 +/- 0.58, 2.78 +/- 0.84, 3.24 +/- 1.00 for septic abscess and 2.37 +/- 0.39, 2.10 +/- 0.38, 1.97 +/- 0.34, 1.82 +/- 0.25, 1.65 +/- 0.23 for aseptic abscess. The 99mTc-CFT uptake was significantly higher in the septic abscess than in sterile one (p < 0.05). The 99mTc-CFT uptake in the septic abscess remains stable or increases until along the 6 h. The 99mTc-CFT uptake in the aseptic abscess decreases along the time. CONCLUSIONS: The scintigraphy with 99mTc-CFT seems able to differentiate sterile inflammation from infection. High biliary excretion limits its application in abdomen. Main application could be diagnosis of osteoarticular infection.
Assuntos
Abscesso/diagnóstico por imagem , Ceftizoxima/análogos & derivados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Abscesso/microbiologia , Animais , Ceftizoxima/farmacocinética , Diagnóstico Diferencial , Compostos de Organotecnécio/farmacocinética , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Sprague-DawleyRESUMO
AIM OF THE STUDY: A new method to label antibiotics with 99mTc, using a third generation, wide spectrum cephalosporine (ceftizoxime), is presented. MATERIAL AND METHODS: 2.5 mg of ceftizoxime, 6.25 mg sodium dithionite in sodium bicarbonate buffer (pH=11.4) as a reductor agent, and 300 MBq of 99mTc were used. The final pH was adjusted to 8.4 with NaOH 0.1N. Radiochemical purity was assessed using ITLC-SG/MEK, ITLC-SG/0.9% NaCl and reverse phase HPLC. Biologic activity was assessed with the agar diffusion technique soaked with E. Coli in disks containing 10.5 microg labelled and non-labelled antibiotic. The maintenance of antibiotic activity was assessed by the diameter of the inhibition halos measured after 24 hours of incubation at 37 degrees C. RESULTS: The labelling efficiency was 94.9 +/- 2.4% (n = 20) and the complex was stable up to 6 h post-labelling. The HPLC chromatography showed five peaks: two of them at 1.7-2.0 min, which corresponds to the ceftizoxime derived product (82%-83% of the absorbance and about 90% of the radioactivity) and a third one at 4.7 min which corresponds to the intact ceftizoxime (6% of absorbance). The remaining two peaks appeared at 3.8 and 6.7 min and represented about 7%-8% of the absorbance. The antibiotic activity of the ceftizoxime-derived compound (CDC) was 83% of the unlabelled one. CONCLUSIONS: 1) The labelling method of ceftizoxime described causes a modification in its structure. 2) The 99mTc binds to the newly formed compound with high labelling efficiency and an acceptable shelf life stability. 3) The 99mTc-CDC maintains 83% of the original antibiotic activity and could be used for the detection of in vivo infection.