99mTc-prulifloxacin in artificially infected animals

S. Q. Shah; A. U. Khan; M. R. Khan

doi:10.3413/Nukmed-0334-10-07

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2011; 50(03): 134-140
DOI: 10.3413/Nukmed-0334-10-07

Original article

Schattauer GmbH

^99mTc-prulifloxacin in artificially infected animals

Radiosynthesis and biological evaluation ^99mTc-Prulifloxacin bei artifiziell infizierten Tieren - Radiosynthese und biologische Bewertung

S. Q. Shah

¹Nuclear Medicine Research Laboratory (NMRL), University of Peshawar, NWFP, Pakistan

,

A. U. Khan

²Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad, Pakistan

,

M. R. Khan

³Phytopharmaceutical & Neutraceuticals Research Laboratory (PNRL), University of Peshawar, NWFP, Pakistan

› Author Affiliations

Abstract

Summary

Aim: The radiosynthesis of ^99mTc-Prulifloxacin (^99mTc-PRN) was assessed in terms of stability, binding with Staphylococcus aureus (S. aureus), biodistribution in rats (RT) and scintigraphic profile in rabbits (RB). Animals, material, methods: ^99mTc-PRN was synthesized by mixing 25 μg of stannous fluoride (SnF2) with 18.5 MB of sodium pertechnetate. Thereafter, 0.5 mg of the prufloxacin (PRN) was added to the reaction mixture and the pH was set at 5.1 with 0.01 mol/l HCl. The reaction mixture was incubated at room temperature. The same process was repeated by increasing the concentration of the stannous fluoride from 25 to 250 μg, sodium pertechnetate from 18,5 to 185 MBq and the PRN from 0.5 to 5 mg. The radiochemical stability of the ^99mTc-PRN was investigated in higher concentration of the cystein. In-vitro binding investigation was performed using living and heat killed S. aureus to verify specificity of the ^99mTc-PRN. Biodistribution was evaluated in artificially infected rats and scintigraphic precision in rabbits at different interval. Results: The ^99mTc-RPN prepared by mixing 2 mg of PRN, 74 MBq sodium pertechnetate, 100 μg stannous fluoride at pH 5.4, appeared to be more than 90% stable with a maximum radiochemical yield of 98.15 ± 0.25% at 30 min. The ^99mTc-PRN showed higher stability in serum and satisfactory in-vitro binding to living as compared to heat killed S. aureus. 14.25 ± 0.15% of the injected dose was accumulated in the infected muscle of the model RT. Infected to normal muscle ratio was 5.12 and inflamed to normal muscle was 1.2. The biodistribution was validated by the scintigraphic localization of infection in rabbits. Conclusion: This investigation of ^99mTc-PRN confirmed its momentous radiochemical immovability in saline, serum, preferential in-vitro binding to living bacteria, higher uptake in the infected muscle of model RT and precise localization in the infected muscle of model RB.

Zusammenfassung

Ziel: Die Radiosynthese von ^99mTc-Prulifloxacin (^99mTc-PRN) wurde in Hinblick auf Stabilität, Bindung an Staphylococcus aureus (S. aureus), Bioverteilung in Ratten (RT) und szintigraphisches Profil in Kaninchen (RB) untersucht. Tiere, Material und Methoden: ^99mTc-PRN wurde durch Mischung von 25 μg Zinnfluorid (SnF2) mit 18,5 MBq Natrium-Pertechnetat synthetisiert. Danach wurden dem Reaktionsgemisch 0,5 mg Prulifloxacin (PRN) hinzugefügt, der pH-Wert wurde mit 0,01 mol/l HCl auf 5,1 eingestellt und das Reaktionsgemisch bei Raumtemperatur inkubiert. Unter Erhöhung der Zinnfluorid- (von 25 auf 250 μg), Natrium-Pertechnetat- (18,5 auf 185 MBq) und PRN-Konzentrationen (von 0,5 auf 5 mg) wurde der gleiche Prozess wiederholt. Die radiochemische Stabilität wurde bei den höheren Cysteinkonzentrationen untersucht. Die In-vitro- Bindung wurde in lebenden und durch Hitze abgetöteten S. aureus untersucht, um die Spezifität des ^99mTc-PRN zu prüfen. Die Bioverteilung wurde in artifiziell infizierten Ratten und die szintigraphische Genauigkeit in Kaninchen in unterschiedlichen Zeitabständen beurteilt. Ergebnisse: Das aus 2 mg PRN, 74 MBq Natrium-Pertechnetat und 100 μg Zinnfluorid bei einem pH von 5,4 hergestellte ^99mTc-PRN schien zu mehr als 90% stabil zu sein, mit einer radiochemischen Ausbeute von 98,15 ± 0,25% nach 30 min. ^99mTc-PRN zeigte im Serum eine höhere Stabilität und die In-vitro- Bindung an lebende S. aureus war zufriedenstellender als an hitzegetötete. Im Rattenmodell wurden 14,25 ± 0,15% der injizierten Dosis im infizierten Muskel angereichert. Das Verhältnis infizierter zu normalem Muskel lag bei 5,12 und entzündeter zu normalem Muskel bei 1,2. Die Bioverteilung wurde mittels szintigraphischer Infektionslokalisation in Kaninchen überprüft. Schlussfolgerung: Diese Untersuchung des ^99mTc-PRN bestätigt seine bedeutende radiochemische Unbeweglichkeit in Kochsalzlösung und Serum, seine In-vitro- Bindung vorzugsweise an lebende Bakterien, die höhere Aufnahme in infiziertem Muskel im Rattenmodell und die präzise Lokalisierung im infizierten Muskel im Kaninchenmodell.

Keywords

^99mTc-prulifloxacin - biodistribution - infection imaging

Schlüsselwörter

^99mTc-Prulifloxacin - Bioverteilung - Infektions-bildgebung

Full Text

References

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