18F-MAA 的临床前特征，一种新型的 99mTc-MAA 的 PET 替代物。

Preclinical characterization of 18F-MAA, a novel PET surrogate of 99mTc-MAA.

机构信息

Department of Biomedical imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan.

出版信息

Nucl Med Biol. 2012 Oct;39(7):1026-33. doi: 10.1016/j.nucmedbio.2012.04.008. Epub 2012 Jul 2.

DOI:10.1016/j.nucmedbio.2012.04.008

PMID:22762865

Abstract

INTRODUCTION

(99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) scintigraphy scan is routinely performed for lung perfusion imaging and for the assessment of in vivo distribution of (90)Y-labeled SIR-Spheres prior to selective internal radiation treatment for hepatocellular carcinoma. Positron emission tomography (PET) imaging is superior to gamma scintigraphy in terms of sensitivity, spatial resolution and accuracy of quantification. This study reported that (18)F-labeled macroaggregated albumin ((18)F-MAA) is an ideal PET imaging surrogate for (99m)Tc-MAA.

METHODS

(18)F-MAA was prepared from the commercial MAA kit via a one-step conjugation with N-succinimidyl 4-(18)F-fluorobenzoate ((18)F-SFB). The biodistribution study and microPET/microSPECT imaging were conducted in normal SD rats after intravenous injection of (18)F-MAA/(99m)Tc-MAA. A comparison study of these two radiotracers was performed after co-injection via the intrahepatic arterial in a N1S1 hepatoma-bearing SD rat model.

RESULTS

The optimal condition for (18)F-MAA preparation is coupling MAA (0.5mg) with (18)F-SFB at 45°C for 5 min in a phosphate buffer of pH 8.5. (18)F-MAA was prepared in 60 min with high radiochemical yield (30%-35%) and high radiochemical purity (>95%). The in vivo distribution of (18)F-MAA after intravenous injection meets the specifications of MAA depicted in European Pharmacopeia. Our study demonstrated excellent correlation between (18)F-MAA and (99m)Tc-MAA in the regional distribution of tumor, liver and lungs (R(2)=0.965, 0.886 and 0.991, respectively), and also in the tumor-to-liver and tumor-to-lungs ratio (R(2)=0.965 and 0.987, respectively) in a N1S1 hepatoma-bearing SD rat model. The organ uptakes derived from animal PET/CT and SPECT/CT imaging after administration of these two tracers were in accordance with those obtained in the distribution studies.

CONCLUSIONS

Starting from commercial MAA kit, an efficient preparation of (18)F-MAA was successfully established. Highly correlated, almost parallel, regional distribution of (18)F-MAA and (99m)Tc-MAA in both normal rats and hepatoma-bearing rats was observed. The findings, taken together, demonstrate that (18)F-MAA is an ideal surrogate for (99m)Tc-MAA for clinical PET applications.

摘要

简介

（99m）Tc 标记的巨聚合白蛋白（（99m）Tc-MAA）闪烁扫描术常用于肺灌注成像，以及评估 90Y 标记的 SIR-Spheres 在选择性内部放射治疗肝细胞癌之前的体内分布。正电子发射断层扫描（PET）成像在灵敏度、空间分辨率和定量准确性方面优于伽马闪烁扫描。这项研究表明，（18）F 标记的巨聚合白蛋白（（18）F-MAA）是（99m）Tc-MAA 的理想 PET 成像替代物。

方法

通过 N-琥珀酰亚胺基 4-（18）F-氟代苯甲酸酯（（18）F-SFB）与商业 MAA 试剂盒中的 MAA 进行一步偶联，制备（18）F-MAA。在静脉注射（18）F-MAA/（99m）Tc-MAA 后，在正常 SD 大鼠中进行了（18）F-MAA 的生物分布研究和 microPET/microSPECT 成像。在 N1S1 肝癌荷瘤 SD 大鼠模型中，通过肝内动脉共注射，对这两种示踪剂进行了比较研究。

结果

（18）F-MAA 制备的最佳条件是在 pH8.5 的磷酸盐缓冲液中，在 45°C 下将 MAA（0.5mg）与（18）F-SFB 偶联 5min。（18）F-MAA 在 60min 内即可制备完成，具有较高的放射化学产率（30%-35%）和较高的放射化学纯度（>95%）。静脉注射（18）F-MAA 后的体内分布符合欧洲药典中 MAA 的规定。我们的研究表明，在 N1S1 肝癌荷瘤 SD 大鼠模型中，（18）F-MAA 与（99m）Tc-MAA 在肿瘤、肝脏和肺部的区域分布（R2=0.965、0.886 和 0.991）以及肿瘤-肝脏和肿瘤-肺部的比值（R2=0.965 和 0.987）上具有极好的相关性。从这两种示踪剂给药后的动物 PET/CT 和 SPECT/CT 成像中获得的器官摄取与分布研究中获得的结果一致。