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

本研究的目的是开发一种新的氨基酸类似物O-[11C]甲基-L-酪氨酸(OMT)，并首次将其应用于全身成像和脑肿瘤成像。首先通过L-酪氨酸与三氟酸甲酯的甲基化，然后通过高效液相纯化，以高放化学产率制备了OMT(岩田等人，2002年)。后来，使用固相萃取而无需高效液相纯化的简单自动化方法被开发用于常规临床(Ishikawa等人，2005年)。17名患者(男性13例，女性4例，平均年龄69岁，范围46-89岁)进行了OMT-PET研究，这些患者包括24个病灶，各种类型的癌症或可疑癌症。16例患者在一周内接受了FDG-PET检查，其诊断准确率分别为：OMT 75%(12/16)和FDG 94%(15/16)；特异性75%(6/8)和FDG 43%(3/7)；OMT 75%(18/24)和FDG 78%(18/23)。慢性黄色肿瘤性胆囊炎显示r-…更喜欢FDG摄取，但OMT没有显著摄取。肺癌和脑肿瘤的肿瘤本底比(T/B值)在2.0左右。OMT-PET和FDG-PET对良恶性病变的SUV均值分别为：恶性2.26±1.44(n=16)，良性2.25±1.33(n=8)，恶性5.98±3.38(n=16)，良性4.79±2.64(n=7)。无论是FDG还是OMT，在良、恶性之间均无显著差异。由于OMT呈正态分布，肝脏和胰腺摄取较轻，但从注射后早期即可观察到尿液排泄。正常的大脑摄取量低于肝脏，略高于肌肉。肾脏和膀胱中的尿液活性最高。研究结果如下：1.肿瘤对OMT的摄取倾向于低于FDG。炎症对OMT的摄取倾向于低于FDG。在一些肿瘤中，如食道癌、胆囊癌，OMT-PET可能有助于避免由于FDG摄取活动性炎症而产生的假阳性结果。较少

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