Dresselaers T, Theys J, Nuyts S, Wouters B, de Bruijn E, Anné J, Lambin P, Van Hecke P, Landuyt W
Biomedical NMR Unit, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Br J Cancer. 2003 Nov 3;89(9):1796-801. doi: 10.1038/sj.bjc.6601345.
The aim of this study was to evaluate the applicability of fluorine-19 magnetic resonance spectroscopy ((19)F MRS) for monitoring in vivo the conversion of 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) after using an attenuated Salmonella Typhimurium strain recombinant to provide cytosine deaminase (TAPET-CD). The (19)F MRS measurements were done on mice bearing the human colon tumour xenograft (HCT116). The intratumoural conversion is greater when TAPET-CD/5-FC is delivered intratumourally (i.tu.) than when TAPET-CD is delivered intravenously (i.v.) and 5-FC intraperitoneally (i.p.). Repeat measurements of the same tumour also yielded important information on the tumour colonization by TAPET-CD through the correlated 5-FC to 5-FU conversion efficacy. The in vivo MRS spectra were confirmed by in vitro (19)F MRS of perchloric acid extracts of the tumour tissue. No 5-FU metabolites were detectable in vivo in the tumours. However, the in vitro measurements revealed, besides 5-FC and 5-FU, the presence of small amounts of catabolites. Finally, spectra obtained in vitro from liver extracts of tumour-bearing mice treated i.tu. with TAPET-CD/5-FC showed no 5-FU and only little amounts of catabolites. Our data illustrate most importantly the potential of (19)F MRS to monitor biologically-based treatments involving cytosine deaminase.
本研究的目的是评估氟-19磁共振波谱（（19）F MRS）在使用减毒鼠伤寒沙门氏菌重组菌株提供胞嘧啶脱氨酶（TAPET-CD）后，对体内5-氟胞嘧啶（5-FC）向5-氟尿嘧啶（5-FU）转化进行监测的适用性。（19）F MRS测量在携带人结肠肿瘤异种移植瘤（HCT116）的小鼠上进行。当肿瘤内注射TAPET-CD/5-FC时，肿瘤内转化率高于静脉注射TAPET-CD并腹腔注射5-FC时。对同一肿瘤的重复测量也通过相关的5-FC到5-FU转化效率，提供了关于TAPET-CD在肿瘤中定植的重要信息。体内MRS光谱通过肿瘤组织高氯酸提取物的体外（19）F MRS得到证实。在肿瘤体内未检测到5-FU代谢物。然而，体外测量显示，除了5-FC和5-FU外，还存在少量分解代谢物。最后，对经肿瘤内注射TAPET-CD/5-FC治疗的荷瘤小鼠肝脏提取物进行体外光谱分析，结果显示没有5-FU，只有少量分解代谢物。我们的数据最重要地说明了（19）F MRS在监测涉及胞嘧啶脱氨酶的生物治疗方面的潜力。
