Comparative evaluation of 68Ga-labelled TATEs: the impact of chelators on imaging
Comparative evaluation of 68Ga-labelled TATEs: the impact of chelators on imaging
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68Ga 标记 TATE 的比较评估：螯合剂对成像的影响
DOI：
10.1186/s13550-020-00620-6
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发表时间：
2020-04
期刊：
影响因子：
3.2
通讯作者：
Yue Chen
中科院分区：
文献类型：
--
作者：
Yuxiao Xia;Chengrun Zeng;Yanhong Zhao;Xinyi Zhang;Zibo Li;Yue Chen
背景
靶向生长抑素受体2（SSTR 2）的68 Ga标记肽在治疗神经内分泌肿瘤（NET）患者方面表现出令人鼓舞的结果。除了金属螯合作用外，还发现双功能螯合剂由于其稳定性、电荷、亲水性等方面的差异而影响成像结果。在本工作中，使用NOTA对68 Ga标记的生长抑素类似物（TATE）进行了比较药代动力学评价和成像特征（1，4，7-三氮杂环壬烷-1，4，7-三乙酸）和DOTA（1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸）作为双功能螯合剂（BFCA）。
结果
获得具有高放射化学纯度的68 Ga-NOTA-TATE和68 Ga-DOTA-TATE。孵育3 h后，68 Ga-NOTA-TATE的体外稳定性（≥ 99%）高于68 Ga-DOTA-TATE（≥ 95%）。68 Ga-NOTA-TATE的水溶解度（分配系数，− 1.76 ± 0.06 vs. − 2.72 ± 0.16）和血浆蛋白结合率（12.12% vs. 30.6%）低于68 Ga-DOTA-TATE。在AR 42 J荷瘤小鼠中观察到不同的药代动力学和相当的肿瘤亲和力（1小时内）。健康志愿者成像研究显示这两种显像剂的分布模式相当。然而，两种示踪剂的最大标准化摄取值（SUVmax）在每个器官中不同。两种PET试剂在肾脏中表现出几乎相同的SUVmax值。与68 Ga-DOTA-TATE相比，68 Ga-NOTA-TATE在大多数其他器官中具有较低的SUVmax，包括肝脏（4.2 vs. 10.1），可能是由于较低的蛋白结合率。
结论
68 Ga-NOTA-TATE和68 Ga-DOTA-TATE在AR 42 J小鼠模型中显示出相当的肿瘤摄取。初步临床研究显示，68 Ga-NOTA-TATE可能降低了主要器官（如肝脏）的背景摄取。尽管受试者数量有限，但仍有必要对68 Ga-NOTA-TATE进行进一步研究，以检测SSTR 2阳性神经内分泌肿瘤。
Background
68Ga-labelled peptides targeting somatostatin receptor 2 (SSTR2) have demonstrated encouraging results in managing patients with neuroendocrine tumours (NETs). In addition to metal chelation, bifunctional chelators have also been found to impact imaging outcomes due to their differences in stability, charge, hydrophilicity, etc. In the present work, a comparative pharmacokinetic evaluation and imaging characteristics were performed between 68Ga-labelled somatostatin analogues (TATE) using NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) as bifunctional chelating agents (BFCAs).
Results
Both 68Ga-NOTA-TATE and 68Ga-DOTA-TATE were obtained with high radiochemical purity. 68Ga-NOTA-TATE demonstrated higher in vitro stability (≥ 99%) than 68Ga-DOTA-TATE (≥ 95%) after 3 h of incubation. The water solubilities (partition coefficients, − 1.76 ± 0.06 vs. − 2.72 ± 0.16) and plasma protein binding rates (12.12% vs. 30.6%) were lower for 68Ga-NOTA-TATE than for 68Ga-DOTA-TATE. Differential pharmacokinetics and comparable tumour affinities (within 1 h) were observed in AR42J tumour-bearing mice. Healthy volunteer imaging studies showed comparable distribution patterns of these two imaging agents. However, the maximum standardized uptake values (SUVmax) of the two tracers varied in each organ. The two PET agents demonstrated almost identical SUVmax values in the kidneys. 68Ga-NOTA-TATE did have a lower SUVmax in most other organs compared with 68Ga-DOTA-TATE, including the liver (4.2 vs. 10.1), potentially due to the lower protein binding rate.
Conclusion
68Ga-NOTA-TATE and 68Ga-DOTA-TATE demonstrated comparable tumour uptake in an AR42J mouse model. An initial clinical study revealed that 68Ga-NOTA-TATE may have reduced background uptake in the major organs such as the liver. Although the subject numbers were limited, further investigation of 68Ga-NOTA-TATE is warranted for detecting SSTR2-positive neuroendocrine tumours.
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DOI：
10.1007/s00259-016-3395-4
发表时间：
2016-10
影响因子：
9.1
作者：
Virgolini, Irene;Gabriel, Michael;Kroiss, Alexander;von Guggenberg, Elisabeth;Prommegger, Rupert;Warwitz, Boris;Nilica, Bernhard;Roig, Ilanos Geraldo;Rodrigues, Margarida;Uprimny, Christian
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5.3
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影响因子：
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作者：
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通讯作者：
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影响因子：
1.5
作者：
Shastry, Manu;Kayani, Irfan;Bomanji, Jamshed B.
通讯作者：
Bomanji, Jamshed B.
影响因子：
28.4
作者：
Dasari, Arvind;Shen, Chan;Yao, James C.
通讯作者：
Yao, James C.