Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor-Positive Tumors
Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor-Positive Tumors
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DOI：
10.2310/7290.2010.00032
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发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Boerman, Otto C.
中科院分区：
文献类型：
--
作者：
Brom, Maarten;Joosten, Lieke;Boerman, Otto C.
与生长抑素受体显像相比，使用In-111-DTPA-小胃泌素（MG 0）的胃泌素受体显像在诊断神经内分泌肿瘤方面显示出附加价值。我们研究了Ga-68标记的胃泌素类似物DOTA-MG 0是否适用于正电子发射断层扫描（PET），这可以提高图像质量。使用AR 42 J大鼠肿瘤细胞系研究了用In-111或Ga-68标记的DOTA-MG 0体外靶向胆囊收缩素-2（CCK 2）/胃泌素受体阳性肿瘤细胞。在具有皮下AR 42 J肿瘤的BALB/c裸鼠中检查生物分布。使用临床前PET计算机断层扫描仪进行体内PET成像。DOTA-MG 0在体外显示出高的受体亲和力。生物分布研究显示Ga-68-DOTA-MG 0的高肿瘤摄取：注射后1小时为4.4 +/-1.3%ID/g。过量未标记肽的共同给药阻断了肿瘤摄取（0.7 +/-0.1%ID/g），表明CCK 2/胃泌素受体介导的摄取（p = .0005）。Ga-68-DOTA-MG 0的生物分布与In-111-DOTA-MG 0相似。皮下和腹膜内肿瘤通过用5 MBq Ga-68-DOTA-MG 0的小动物PET成像清晰地可视化。In-111和Ga-68标记的DOTA-MG 0特异性地在CCK 2/胃泌素受体阳性的AR 42 J肿瘤中积累，除了肾脏之外，具有相似的生物分布。通过microPET可以清晰地观察AR 42 J肿瘤。因此，Ga-68-DOTA-MG 0是一种用于人体CCK 2/胃泌素受体阳性肿瘤PET成像的有前途的示踪剂。
In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using In-111-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the Ga-68-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either In-111 or Ga-68 in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of Ga-68-DOTA-MG0: 4.4 +/- 1.3 % ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 +/- 0.1 % ID/g), indicating CCK2/gastrin receptor-mediated uptake (p = .0005). The biodistribution of Ga-68-DOTA-MG0 was similar to that of In-111-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq Ga-68-DOTA-MG0. In-111-and Ga-68-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, Ga-68-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.