Imaging and Pharmacokinetics of 64Cu-DOTA-HB22.7 Administered by Intravenous, Intraperitoneal, or Subcutaneous Injection to Mice Bearing Non-Hodgkin's Lymphoma Xenografts
Imaging and Pharmacokinetics of 64Cu-DOTA-HB22.7 Administered by Intravenous, Intraperitoneal, or Subcutaneous Injection to Mice Bearing Non-Hodgkin's Lymphoma Xenografts
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DOI：
10.1007/s11307-008-0148-1
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发表时间：
2009-03-01
影响因子：
3.1
通讯作者：
Tuscano, Joseph M.
中科院分区：
文献类型：
--
作者：
Martin, Shiloh M.;O'Donnell, Robert T.;Tuscano, Joseph M.
目的：该研究的目的是比较Cu-64-DOTA-HB 22.7在静脉内（IV）、腹膜内（IP）和皮下（SQ）给药于携带异种移植物的小鼠时的肿瘤特异性靶向、药代动力学和生物分布。异种移植靶向通过微型正电子发射断层扫描（microPET）进行评价，并通过器官生物分布研究进行确认。结果：Cu-64-DOTA-HB 22.7在24-48 h内具有相同的肿瘤靶向性。器官生物分布证实了肿瘤特异性靶向。血液药代动力学表明，Cu-64-DOTA-HB 22.7进入血流后IP和SQ管理到类似程度的IV administration.Conclusions，虽然在一个较慢的速度：这些研究结果建立Cu-64-DOTA-HB 22.7作为一个潜在的放射免疫和/或NHL特异性显像剂。这些发现提供了证据，证明IP和SQ给药可以达到与IV给药相当的结果，并可能为基于抗体的治疗提供更有效、可重现的治疗计划。
Purpose: The aim of the study is to compare the tumor-specific targeting, pharmacokinetics, and biodistribution of Cu-64-DOTA-HB22.7 when administered to xenograft-bearing mice intravenously (IV), intraperitoneally (IP),and subcutaneously (SQ).Procedures: Mice bearing human non-Hodgkin's lymphoma (NHL) xenografts were injected IV, IP, or SQ with Cu-64-DOTA-HB22.7. Xenograft targeting was evaluated by micro positron emission tomography (microPET) and confirmed by organ biodistribution studies. Blood measurements of Cu-64 were performed to determine the pharmacokinetics and clearance of Cu-64-DOTA-HB22.7.Results: Cu-64-DOTA-HB22.7 demonstrated equivalent tumor targeting within 24-48 h, regardless of the route of administration. Organ biodistribution confirmed tumor-specific targeting. Blood pharmacokinetics demonstrated that Cu-64-DOTA-HB22.7 accessed the bloodstream after IP and SQ administration to a similar degree as IV administration, albeit at a slower rate.Conclusions: These findings establish Cu-64-DOTA-HB22.7 as a potential radioimmunotherapeutic and/or NHL-specific imaging agent. These findings provide evidence that IP and SQ administration can achieve results equivalent to IV administration and may lead to more efficient, reproducible treatment plans for antibody-based therapeutics.