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First-in-human phase 0 study of 111In-CHX-A"-DTPA trastuzumab for HER2 tumor imaging

  1. Author:
    Kurdziel, K A
    Mena, E
    McKinney, Y
    Wong, K
    Adler,Stephen
    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

  2. Author Address

    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., Genitourinary Malignancies Branch, CCR/NCI, NIH, USA., Division of Nuclear Medicine, Radiology and Imaging Sciences, Clinical Center(CC), NIH, USA., Women 39;s Malignancies Branch, CCR/NCI, NIH, USA., Radiation Oncology Branch, CCR/NCI, NIH, USA., Division of Cancer Treatment and Diagnosis and CCR/NCI, NIH, USA., Laboratory of Pathology, CCR/NCI, NIH, USA.,
    1. Year: 2019
    2. Date: Apr
    3. Epub Date: 2018 07 13
  2. Journal: Journal of translational science
    1. 5
    2. 2
  4. Type of Article: Article
  1. Abstract:

    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, 111In-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. 111In-CHX-A"-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ?-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 t1/2=46.9h (R2=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 (R2 =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 t1/2=34.2h (R2 =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R2=0.96; 95%CI 186.1 to 489.2h). 111In-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 111In-CHX-A"-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.

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External Sources

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  2. DOI: 10.15761/JTS.1000269
  3. PMID: 30906574

Library Notes

  1. Fiscal Year: FY2018-2019
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