Cancer diagnosis with Positron Emission Tomography ; Development of a new tyrosine analogue

研究目的是开发一种新的氨基酸类似物O-[11C]甲基- l-酪氨酸（OMT），并将其首次临床应用于全身成像和脑肿瘤成像。首先用[^<11>C]三氟酸甲酯甲基化l -酪氨酸，然后用高效液相色谱纯化，得到了高放化产率的OMT （Iwata et al., 2002）。后来，无需HPLC纯化的固相萃取简便自动化方法被开发用于常规临床应用（Ishikawa et al., 2005）。本文采用OMT-PET对17例不同类型癌症或疑似癌症患者进行了研究，其中男性13例，女性4例，平均年龄69岁，年龄范围46 ~ 89岁，共24个病灶。16名患者也在一周内用FDG-PET进行了研究。所有病变的诊断准确率计算如下：OMT敏感性75% (12/16)，FDG敏感性94% (15/16)；OMT特异性75% (6/8)，FDG特异性43% (3/7)；OMT准确率75% (18/24)，FDG准确率78%（18/23）。慢性黄瘤性胆囊炎表现为FDG摄取较多，OMT摄取不明显。肺癌和脑肿瘤的肿瘤与背景比（T/B）均在2.0左右。OMT- pet、FDG- pet对良、恶性病变的平均SUV值分别为：OMT恶性（2.26±1.44）（n=16）、OMT良性（2.25±1.33）（n=8）、FDG恶性（5.98±3.38）（n=16）、FDG良性（4.79±2.64）（n=7）。无论是FDG还是OMT，良恶性之间均无显著差异。OMT呈正态分布，肝脏和胰腺摄取较轻，但注射后早期可见尿排泄。正常的大脑摄取比肝脏低，略高于肌肉。肾脏和膀胱中的尿液活性最高。结果总结如下：1。肿瘤对OMT的摄取倾向于低于fdg2。炎症对OMT的摄取倾向于低于fdg。在某些肿瘤中，如食管癌、胆囊癌，OMT-PET可能有助于避免因FDG摄取活动性炎症而产生的假阳性结果。少

The aim of study is the development of a new amino acid analogue O-[11C]methyl-L-tyrosine (OMT) and its first clinical application to whole-body imaging as well as brain tumor imaging. OMT was firstly prepared with a high radiochemical yield by the methylation of L-tyrosine with [^<11>C]methyl triflate followed by HPLC purification (Iwata et al., 2002). Later, the simple automated method using the solid phase extraction without HPLC purification was developed for routine clinical use (Ishikawa et al., 2005).Seventeen patients (13 male, 4 female, mean age 69, range 46-89) of various types of cancer or suspected of cancer with 24 lesions were studied with OMT-PET. Sixteen patients have been studied with FDG-PET also within a week.Diagnostic accuracy for all lesions were calculated as follows : sensitivity of OMT 75% (12/16) and FDG 94% (15/16) ; specificity of OMT 75% (6/8) and FDG 43% (3/7) ; and accuracy of OMT 75% (18/24) and FDG 78% (18/23). Chronic xantomatous cholecystitis showed r … More ing like uptake with FDG, but no significant uptake with OMT. Tumor to background ratios (T/B ratios) of lung cancer and brain tumor were around 2.0. Mean SUV values of malignant and benign lesions with OMT-PET and FDG-PET were as follows : OMT malignant 2.26±1.44 (n=16), OMT benign 2.25±1.33 (n=8), FDG malignant 5.98±3.38 (n=16), FDG benign 4.79±2.64 (n=7). There were no significant differences between malignant and benign neither with FDG nor OMT.As the normal distribution, liver and pancreas uptake of OMT was mild, but urinary excretion was observed from early after injection. Normal brain uptake was lower than the liver, and slightly higher than the muscle. Kidney and urine in the bladder showed the highest activity. Results were summarized as follows;1. OMT uptake by tumor was tended lower than the FDG.2. OMT uptake by inflammation was tended lower than the FDG.3. In some tumors, such as esophageal cancer, gall bladder cancer, OMT-PET may be helpful to avoid false positive results that was derived by FDG uptake of active inflammation. Less