Abstract
Purpose: Purpose of this study is to synthesize $^{99m}Tc$-labeled transferrin for injection imaging and to compare it with $^{67}Ga$-titrate for the detection of infectious foci. Materials and methods: Succinimidyl 6-hydrazino-nicotinate hydrochloride-chitosan-transferrin (Transferrin) was synthesized and radiolabeled with $^{99m}Tc$. Labeling efficiencies of $^{99m}Tc$-Transferrin were determined at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr. Biodistribution and imaging studies with $^{99m}Tc$-Transferrin and $^{67}Ga$-citrate were performed in a rat abscess model induced with approximately $2{\times}10^8$ colony forming unit of Staphylococcus aureus ATCC 25923. Results: Successful synthesis of Transferrin was confirmed by mass spectrometry. Labeling efficiency of $^{99m}Tc$-Transferrin was $96.2{\pm}0.7%,\;96.4{\pm}0.5%,\;96.6{\pm}1.0%,\;96.9{\pm}0.5%,\;97.0{\pm}0.7%\;and\;95.5{\pm}0.7%$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr, respectively. The injected dose per tissue gram of $^{99m}Tc$-Transferrin was $0.18{\pm}0.01\;and\;0.18{\pm}0.01$ in the lesion and $0.05{\pm}0.01\;and\;0.04{\pm}0.01$ in the normal muscle, and lesion-to-normal muscle uptake ratio was $3.7{\pm}0.6\;and\;4.7{\pm}0.4$ at 30 min and 3 hr, respectively. On image, lesion-to-background ratio of $^{99m}Tc$-Transferrin was $2.18{\pm}0.03,\;2.56{\pm}0.11,\;3.08{\pm}0.18,\;3.77{\pm}0.17,\;4.70{\pm}0.45\;and\;5.59{\pm}0.40$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 10 hr and those of $^{67}Ga$-citrate was $3.06{\pm}0.84,\;4.12{\pm}0.54\;and\;4.55{\pm}0.74 $ at 2 hr, 24 hr and 48 hr, respectively. Conclusion: Transferrin is successfully labeled with $^{99m}Tc$, and its labeling efficiency was higher than 95% and stable for 8 hours. $^{99m}Tc$-Transferrin scintigraphy showed higher image quality in shorter time compared to $^{67}Ga$-citrate image. $^{99m}Tc$-transferrin is supposed to be useful in the detection of the infectious foci.
목적 : 본 연구의 목적은 $^{99m}Tc$-방사성표지 트렌스페린 ($^{99m}Tc$-transferrin)을 개발하여 감염/염증병소의 진단에 이용할 수 있는지 알아보고, 이를 $^{67}Ga$-Citrate 영상과 비교하고자 하였다. 대상 및 방법 : Succinimidyl 6-hydrazino-nicotinate hydrochloride -chitosan -transferrin (Transferrin)을 합성하고, 여기에 $^{99m}Tc$ 방사성 표지를 시행하였다. $^{99m}Tc$-transferrin의 방사성표지효율은 표지 후 10분, 30분, 1시간, 2시간, 4시간, 8시간에 측정하였다. 포도상구균(ATCC 25923, $2{\times}10^8$ colony forming unite, 0.2 ml)을 접종한 쥐농양모델에서 $^{99m}Tc$-transferrin과 $^{67}Ga$-citrate의 생체내 분포를 평가하고 영상 검사를 실시하였다. 결과: 질량분석계를 이용하여 Transferrin이 성공적으로 제조되었음을 알 수 있었다. $^{99m}Tc$-transferrin의 방사성표지효율은 10분, 30분, 1시간, 2시간, 4시간, 8시간에 각각 $96.2{\pm}0.7%,\;96.4{\pm}0.5%,\;96.6{\pm}1.0%,\;96.9{\pm}0.5%,\;97.0{\pm}0.7%\;and\;95.5{\pm}0.7%$ 이었다. $^{99m}Tc$-transferrin의 단위섭취량은 감염병소에서 $0.18{\pm}0.01\;and\;0.18{\pm}0.01$, 정상근육에서 $0.05{\pm}0.01\;and\;0.04{\pm}0.01$이었고, 감염병소 대 정상근육 섭취비는 30분과 3시간에 각각 $3.7{\pm}0.6\;and\;4.7{\pm}0.4$이었다. $^{99m}Tc$-transferrin 영상에서 10분, 30분, 1시간, 2시간, 4시간 그리고 10시간에서의 병소/배후방사능비는 각각 $2.18{\pm}0.03,\;2.56{\pm}0.11,\;3.08{\pm}0.18,\;3.77{\pm}0.17,\;4.70{\pm}0.45$ 그리고 $5.59{\pm}0.40$이었고, $^{67}Ga$-citrate의 경우 2시간, 24시간, 48시간에 $3.06{\pm}0.84,\;4.12{\pm}0.54\;4.55{\pm}0.74 $이었다. 결론 : Transferrin에 $^{99m}Tc$을 이용한 방사성표지가 성공적으로 이루어졌고, $^{99m}Tc$-transferrin의 표지효율은 8시간까지 95% 이상의 안정된 방사성표지효율을 보였다. $^{99m}Tc$-transferrin을 이용한 감염영상을 성공적으로 얻을 수 있었으며, $^{67}Ga$-citrate 영상과 비교하여 더 빠른 시간 안에 우수한 영상을 얻을 수 있었다. 그러므로 $^{99m}Tc$-transierrin이 감염 병소의 영상진단에 사용될 수 있을 것으로 기대된다.