Biodistribution of 3-[$^{131}I$]iodo-O-methyl-L-${\alpha}$-methyltyrosine in Tumor Bearing Rats: A Comparison Study with L-3-[$^{131}I$]iodo-${\alpha}$-methyltyrosine

종양 이식 백서에서 3-[$^{131}I$iodo-O-methyl-L-${\alpha}$-methyltyrosine의 체내 동태 연구: L-3-[$^{131}I$iodo-${\alpha}$-methyltyrosine와 비교

Purpose : The aim of this study was to evaluate the feasibility of 3-[$^{131}I$]iodo-O-methyl-L-${\alpha}$-methyltyrosine ([$^{131}I$]OMIMT) as an agent for tumor image. Materials and Methods : After synthesis of 4-O-methyl-L-${\alpha}$-methyltyrosine (OMAMT), OMAMT was labeled with [$^{131}I$] using Iodogen method. In vitro cellular uptake study was performed using 9 L gliosarcoma cells at various time points upto 4 hr. The biodistribution (five rats implanted with the 9 L gliosar-coma cells per group) was evaluated at 30 min, 2 hr, 24 hr after iv injection of 3.7 MBq [$^{131}I$]OMIMT or L-3-[$^{131}I$]iodo-${\alpha}$-methyltyrosine [$^{131}I$]IMT). Gamma camera images were obtained at 30 min, 2 hr and 24 hr. Results: [$^{131}I$]OMIMT uptake was 3.3 times and 2.5 times higher than [$^{131}I$]IMT uptake at 30 min and 60 min, respectively and same after 2 hr in in vitro study using 9L gliosarcoma cells. Maximum accumulation in tumor occurred at 30 min for both [$^{131}I$]OMIMT and [$^{131}I$]IMT in tumor bearing rats. The tumor uptake of [$^{131}I$]OMIMT was significantly higher than that of [$^{131}I$]IMT at early time point studied ($3.74{\pm}0.48$ vs $0.38{\pm}0.17%$ ID/g at 30 min and $2.40{\pm}0.17$ vs $0.24{\pm}0.03%$ ID/g at 2 hr, respectively, p<0.01). However, the tumor uptake of both radiolabels were not significantly different at 24 hr ($0.04{\pm}0.01$ vs $0.05{\pm}0.01%$ ID/g). Tumor was visualized as early as at 30 min in gamma camera images. Conclusion: These data suggested that [$^{131}I$]OMIMT might be a useful tumor imaging agent and has more advantage for the tumor imaging compared to [$^{131}I$]IMT

목적 : 본 연구는 3-[$^{131}I$]iodo-O-methyl-L-${\alpha}$-methyltyrosine ([$^{131}I$]OMIMT)의 종양영상용 방사성의 약품으로서의 유용성을 알고자 시행하였다. 대상 및 방법 : [$^{131}I$]OMIMT는 4-0-methyl-L-${\alpha}$-methyltyrosine (OMAMT)를 lodogen 방법으로 [$^{131}I$]를 표지하여 얻었다. 9 L gliosarcoma 세포주를 배양한 다음 in vitro에서 [$^{131}I$]OMIMT와 L-3-[$^{131}I$]iodo-${\alpha}$-methyltyrosine ([$^{131}I$]IMT)의 세포섭취율을 4시간까지 구하였다. 같은 세포주를 Fischer 백서의 우대퇴부에 이식하여 종괴를 형성한 다음 [$^{131}I$]OMIMT와 [$^{131}I$]IMT를 각각 주사하고 30분, 2시간, 24시간에 동물을 희생하여 종양내의 섭취와 체내분포를 조직gram당 주사량의 백분율(% ID/g)을 구하였다. 또한 종양이식 백서에 [$^{131}I$]OMIMT 1.11 MBq을 정맥주사하고 30분, 2시간, 24시간 후 감마카메라로 영상을 얻었다. 결과: 9 L glioma 세포의 [$^{131}I$]OMIMT 섭취는 30분에 최고점에 도달하고 이 후 4시간까지 감소하였으며, [$^{131}I$]IMT에 비하여 배양 후 30분에서 3.3배(6.7% vs 2.3% uptake) 높았으나 4시간에는 차이가 없었다. [$^{131}I$]OMIMT의 체내 종양내의 섭취를 [$^{131}I$]IMT와 비교하였을 때, 주사 후 30분과($3.74{\pm}0.48$ vs $0.38{\pm}0.17%$ ID/g, p<0.01), 2시간($2.40{\pm}0.17$ vs $0.24{\pm}0.03%$ ID/g, p<0.01)에 유의하게 높은 섭취를 보였고, 24시간($0.04{\pm}0.01%$ ID/g)까지 감소하였다. 종양이식백서에서 [$^{131}I$]OMIMT 주사 후 30분 영상에서 종양을 관찰할 수 있었다. 결론: [$^{131}I$] 또는 [$^{131}I$]OMIMT는 종양의 아미노산 대사 영상제제로 이용될 수 있으며 앞으로 이에 대한 임상연구가 필요할 것으로 생각되었다.