双胞胎在精神——第一集:比较临床前评价(68)Ga DOTATATE和HA-DOTATATE Ga (68)。

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Schottelius M, Simecek J,霍夫曼F, Willibald M, Schwaiger M,西风HJ

双胞胎在精神——第一集:比较临床前评价(68)Ga DOTATATE和HA-DOTATATE Ga (68)。

EJNMMI研究》2015年4月10日,犯规。doi: 10.1186 / s13550 - 015 - 0099 - x。eCollection 2015。

PubMed ID
25918675 (在PubMed
]
文摘

背景:最近,intra-patient比较表明,生长抑素(sst)配体((68)Ga) HA-DOTATATE (((68) Ga) DOTA-3-iodo-Tyr (3) -octreotate)提供宠物图像相当于或优于同DOTATATE Ga (68)。提供一个全面的基础不过示踪biodistribution和剂量测定法,观察细微差异的特点[(68)Ga] HA-DOTATATE在详细调查临床前研究。方法:亲和力(nat) Ga-HA-DOTATATE和(nat) Ga-DOTATATE sst1-5测定使用膜制剂和[(125)我]SST-28放射性配体。内化成AR42J细胞是研究dual-tracer研究[(125)我]TOC作为内部参考。Biodistribution研究使用AR42J带有CD1小鼠和特异性的示踪剂摄取在竞争研究证实coinjection TOC 0.8毫克/公斤。结果:Sst2亲和力(IC50) ((nat) Ga) HA-DOTATATE (1.4 + / - 0.8 nM, logP: -3.16)和((nat) Ga) DOTATATE (1.2 + / - 0.6 nM, logP: -3.69)几乎是相同的。两化合物显示IC50 sst1妈妈> 1,3,4,sst5亲和力显著增加(nat) Ga-HA-DOTATATE (102 + / - 65 nM vs > 1 (nat) Ga-DOTATATE妈妈)。陆(nat) HA-DOTATATE和[陆(nat)] DOTATATE显示略低,相同sst2亲和力(2.0 + / - 1.6和2.0 + / - 0.8 nM,分别)和sst3亲和力93 + / - 1和162 + / - 16 nM。[(68)Ga]的内化HA-DOTATATE高出十倍比[(125)我]TOC但只有6倍高(68)Ga DOTATATE和HA-DOTATATE陆(177)。[(68)Ga] HA-DOTATATE和[(68)Ga] DOTATATE显示类似的目标和非目标吸收患者,biodistribution研究老鼠1 h后注入(n = 5)显示略有增加(Ga(68))的非特异性吸收HA-DOTATATE在血液、肝脏和肠道(0.7 + / - 0.3,1.0 + / - 0.2,和4.0 + / - 0.7% iD / g和0.3 + / - 0.1,0.5 + / - 0.1,和2.7 + / - 0.8%的iD / g (68) Ga DOTATATE)。 However, sst-mediated accumulation of [(68)Ga]HA-DOTATATE in the pancreas, adrenals, and tumor was significantly enhanced (36.6 +/- 4.3, 10.8 +/- 3.2, and 33.6 +/- 10.9 %iD/g vs 26.1 +/- 5.0, 5.1 +/- 1.4, and 24.1 +/- 4.9 %iD/g, respectively). Consequently, tumor/background ratios for [(68)Ga]HA-DOTATATE in the AR42J model are comparable or slightly increased compared to [(68)Ga]DOTATATE. CONCLUSIONS: The present preclinical data fully confirm the general biodistribution pattern and excellent in vivo sst-targeting characteristics previously observed for [(68)Ga]HA-DOTATATE in patients. The effect of slightly enhanced lipophilicity on background accumulation and normal organ dose is compensated by the high uptake of [(68)Ga]HA-DOTATATE in tumor. Thus, [(68)Ga]HA-DOTATATE represents a fully adequate, freely available substitute for [(68)Ga]DOTATATE and, given the superb sst-targeting characteristics of [(177)Lu]HA-DOTATATE in vitro, potential applicability for sst-targeted PRRT.

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