Kurdziel K A, Mena E, McKinney Y, Wong K, Adler S, Sissung T, Lee J, Lipkowitz S, Lindenberg L, Turkbey B, Kummar S, Milenic D E, Doroshow J H, Figg W D, Merino M J, Paik C H, Brechbiel M W, Choyke P L
Molecular Imaging Program (MIP), Center for Cancer Research (CCR)/National Cancer Institute (NCI), National Institutes of Health (NIH), USA.
Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, USA.
J Transl Sci. 2019 Apr;5(2). doi: 10.15761/JTS.1000269. Epub 2018 Jul 13.
Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, In-CHX-A"-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status.
In-CHX-A"-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ɣ-camera (n=6) and/or SPECT (n=8) imaging sessions.
No safety issues were identified. Visual and semi-quantitative imaging data were concordant with tissue HER2 expression profiling in all but 1 patient. The biodistribution showed intense peak liver activity at the initial imaging timepoint (3.3h) and a single-phase clearance fit of the average time-activity curve (TAC) estimated t=46.9h (R=0.97; 95%CI 41.8 to 53h). This was followed by high gastrointestinal (GI) tract activity peaking by 52h. Linear regression predicted GI clearance by 201.2h (R =0.96; 95%CI 188.5 to 216.9h). Blood pool had lower activity with its maximum on the initial images. Non-linear regression fit projected a t=34.2h (R =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R=0.96; 95%CI 186.1 to 489.2h).
In-CHX-A"-DTPA trastuzumab can be safely imaged in humans. The biodistribution allowed for visual and semiquantitative analysis with results concordant with tissue expression profiling in 10 of 11 patients. Advances in Knowledge and Implications for Patient Care Using readily available components and on-site radiolabeling In-CHX-A"-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.
过度表达人表皮受体2（HER2）或其原癌基因出现扩增或突变的肿瘤患者预后较差。使用曲妥珠单抗和/或其他HER2靶向疗法可提高HER2阳性肿瘤患者的总生存率，因此准确识别可能受益的患者至关重要。我们报告了一项针对已知HER2状态患者的0期成像剂In-CHX-A"-DTPA曲妥珠单抗研究，以评估其安全性和生物分布，并获取有关其提供准确、全身、非侵入性手段来确定HER2状态能力的初步数据。
In-CHX-A"-DTPA曲妥珠单抗在现场进行放射性标记，并缓慢注入11例患者体内，这些患者接受了单次（n = 5）或多次（n = 6）γ相机（n = 6）和/或SPECT（n = 8）成像检查。
未发现安全问题。除1例患者外，视觉和半定量成像数据与组织HER2表达谱一致。生物分布显示在初始成像时间点（3.3小时）肝脏活性出现强烈峰值，平均时间-活性曲线（TAC）的单相清除拟合估计t = 46.9小时（R = 0.97；95%CI 41.8至53小时）。随后胃肠道（GI）活性较高，在52小时达到峰值。线性回归预测胃肠道清除时间为201.2小时（R = 0.96；95%CI 188.5至216.9小时）。血池活性较低，在初始图像上达到最大值。非线性回归拟合预测t = 34.2小时（R = 0.96；95%CI 25.3至46.3小时）。假设全身清除呈线性，线性回归预测在256.5小时完全清除（x轴截距）（R = 0.96；95%CI 186.1至489.2小时）。
In-CHX-A"-DTPA曲妥珠单抗可在人体中安全成像。生物分布允许进行视觉和半定量分析，11例患者中有10例的结果与组织表达谱一致。知识进展及对患者护理的意义 使用现成组件和现场放射性标记，In-CHX-A"-DTPA曲妥珠单抗SPECT成像可能提供一种经济、非侵入性的方法来检测HER2过表达。
