Preclinical Characterization of 5-Amino-4-Oxo-[6-11C]Hexanoic Acid as an Imaging Probe to Estimate Protoporphyrin IX Accumulation Induced by Exogenous Aminolevulinic Acid

Journal of Nuclear Medicine

Hitomi Sudo¹  Tatsuya Kikuchi¹  Maki Okada¹  Chie Suzuki¹  Aya Sugyo¹  Atsushi B. Tsuji¹  Koichi Kato¹  Ming-Rong Zhang¹  Tsuneo Saga¹  Yasushi Arano¹ 

关键词: 5-aminolevulinic acid;    photodynamic therapy;    sonodynamic therapy;    aminolevulinic acid dehydratase;    ¹¹C-MALA;   

DOI  :  10.2967/jnumed.114.145086

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Preoperative noninvasive imaging to estimate the quantity and spatial distribution of protoporphyrin IX (PpIX) accumulation in tumors induced by 5-aminolevulinic acid (ALA) administration is expected to improve the efficacy of ALA-based fluorescence-guided resection and photo- and sonodynamic therapies. PpIX synthesis from exogenous ALA has been reported to be regulated by ALA influx or ALA dehydratase (ALAD) activity, which catalyzes the first step of the synthesis. In this study, we characterized the properties of a 11C-labeled ALA analog, 5-amino-4-oxo-[6-11C]hexanoic acid (11C-MALA), as a PET tracer to estimate PpIX accumulation. Methods: In vitro uptake of 11C-MALA and 3H-ALA was determined in 5 tumor cell lines after 10-min incubation with each tracer at 37°C. The expression levels of ALAD were determined by Western blot analysis. In vivo distribution and dynamic PET studies were conducted in tumor-bearing mice. In vitro and in vivo accumulation of ALA-induced PpIX was determined by measuring fluorescence in extracts of cells or tumors. Results: In vitro uptake of 11C-MALA in 5 tumor cell lines was correlated with ALAD expression levels and PpIX accumulation. In vivo biodistribution and dynamic PET studies showed that 11C-MALA was rapidly incorporated into tumors, and the tumor-to-muscle ratio of 11C-MALA at 1 min after injection was significantly correlated with that of 3H-ALA. 11C-MALA in tumors was continuously decreased thereafter, and the elimination rate of 11C-MALA from AsPC-1 tumors with the highest ALAD expression level was slower than from other tumors with lower expression levels. These results suggest that the influx and intracellular retention of 11C-MALA reflect ALA influx and ALAD expression levels, respectively. Tumor accumulation of 11C-MALA at 60 min after injection was strongly correlated with PpIX accumulation in tumor tissues. Conclusion: 11C-MALA PET has the potential to noninvasively estimate the quantitative and spatial accumulation of exogenous ALA-induced PpIX.

【 授权许可】

Unknown