Biodistribution of 89Zr-trastuzumab and PET Imaging of HER2-Positive Lesions in Patients With Metastatic Breast Cancer

Dijkers, Eli; Munnink, Thijs H. Oude; Kosterink, Jos G. W.; Brouwers, Adrienne H.; Jager, PL; Jong, Johan R. de; Dongen, Guus Ams van; Schröder, Carolina P.; Hooge, Marjolijn N. Lub-de; Vries, Elisabeth G.E. de

doi:10.1038/clpt.2010.12

Cited by 721 publications

(697 citation statements)

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“…49 Not only has HER2 been exploited as a signaling target via the therapeutic antibody trastuzumab, 50 it has been further utilized as a drug delivery vector in the antibody-drug conjugate trastuzumab emtansine 51 and in clinical imaging of HER2-positive breast cancer. 40–43 It should be noted, however, that HER2 is a somewhat unusual internalizing oncology target in that it exhibits extremely high expression levels and that trastuzumab binding does not down-regulate surface HER2, but instead passively recycles after HER2 endocytosis. 50 …”

Section: Discussionmentioning

confidence: 99%

“…4,23,30 While these early imaging studies were successful, highly expressed non-internalizing targets only represent a fraction of clinically relevant oncology targets since many cell-surface cancer targets are internalizing. For instance, clinical imaging of human epidermal growth factor receptor 2 (HER2)-expressing tumors has been actively pursued via directly labeled antibodies, 40,41 antibody fragments 42 and affibodies 43 in an effort to improve patient selection and response monitoring for HER2-targeted cancer therapies. 44 Fewer examples exist in which internalizing targets have been pretargeted, 20,39 likely due to risk of time-dependent cell surface depletion of TCO moieties available for click reaction through antibody-bound receptor internalization, thereby decreasing image contrast.…”

Section: Introductionmentioning

confidence: 99%

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Site-specific conjugation allows modulation of click reaction stoichiometry for pretargeted SPECT imaging

Mandikian¹,

Rafidi²,

Adhikari³

et al. 2018

mAbs

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Antibody pretargeting is a promising strategy for improving molecular imaging, wherein the separation in time of antibody targeting and radiolabeling can lead to rapid attainment of high contrast, potentially increased sensitivity, and reduced patient radiation exposure. The inverse electron demand Diels-Alder ‘click’ reaction between trans-cyclooctene (TCO) conjugated antibodies and radiolabeled tetrazines presents an ideal platform for pretargeted imaging due to rapid reaction kinetics, bioorthogonality, and potential for optimization of both slow and fast clearing components. Herein, we evaluated a series of anti-human epidermal growth factor receptor 2 (HER2) pretargeting antibodies containing distinct molar ratios of site-specifically incorporated TCO. The effect of stoichiometry on tissue distribution was assessed for pretargeting TCO-modified antibodies (monitored by 125I) and subsequent accumulation of an 111In-labeled tetrazine in a therapeutically relevant HER2+tumor-bearing mouse model. Single photon emission computed tomography (SPECT) imaging was also employed to assess tumor imaging at various TCO-to-monoclonal antibody (mAb) ratios. Increasing TCO-to-mAb molar ratios correlated with increased in vivo click reaction efficiency evident by increased tumor distribution and systemic exposure of 111In-labeled tetrazines. The pharmacokinetics of TCO-modified antibodies did not vary with stoichiometry. Pretargeted SPECT imaging of HER2-expressing tumors using 111In-labeled tetrazine demonstrated robust click reaction with circulating antibody at ~2 hours and good tumor delineation for both the 2 and 6 TCO-to-mAb ratio variants at 24 hours, consistent with a limited cell-surface pool of pretargeted antibody and benefit from further distribution and internalization. To our knowledge, this represents the first reported systematic analysis of how pretargeted imaging is affected solely by variation in click reaction stoichiometry through site-specific conjugation chemistry.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Site-specific conjugation allows modulation of click reaction stoichiometry for pretargeted SPECT imaging

Mandikian¹,

Rafidi²,

Adhikari³

et al. 2018

mAbs

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“…Current examples of PET imaging to measure target expression include estrogen receptor imaging and androgen receptor imaging; HER2 imaging; imaging angiogenesis nonspecifically by measuring blood flow and by imaging specific components expressed in neovasculature; and measuring novel targets, such as matrix metalloproteinases. [130][131][132][133][134][135] In all of these cases, PET imaging has the potential to provide prognostic information and can help predict the likelihood that a patient will respond to a targeted chemotherapeutic agent. One of the major imaging agents in this class is 18 F-fluoroestradiol (FES), which has exhibited the most promise in quantifying the functional estrogen receptor status of primary or metastatic breast cancer.…”

Section: Imaging Protein and Cell Membrane Metabolismmentioning

confidence: 99%

PET/CT imaging in cancer: Current applications and future directions

Farwell

Pryma

Mankoff

2014

Cancer

196

120

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Positron emission tomography (PET) is a radiotracer imaging method that yields quantitative images of regional in vivo biology and biochemistry. PET, now used in conjunction with computed tomography (CT) in PET/CT devices, has had its greatest impact to date on cancer and is now an important part of oncologic clinical practice and translational cancer research. In this review of current applications and future directions for PET/CT in cancer, the authors first highlight the basic principles of PET followed by a discussion of the biochemistry and current clinical applications of the most commonly used PET imaging agent, 18 F-fluorodeoxyglucose (FDG). Then, emerging methods for PET imaging of other biologic processes relevant to cancer are reviewed, including cellular proliferation, tumor hypoxia, apoptosis, amino acid and cell membrane metabolism, and imaging of tumor receptors and other tumor-specific gene products. The focus of the review is on methods in current clinical practice as well as those that have been translated to patients and are currently in clinical trials. Cancer 2014;120:3433-45.

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“…Dijkers et al demonstrated that PET scanning after administration of 89 Zr-trastuzumab at appropriate doses allows visualization and quantification of uptake in HER-2-positive lesions in patients with metastatic breast cancer, even in the brain [16]. A feasibility study in a greater number of patients (Baum et al and Dijkers et al enrolled only 3 and 14 patients, respectively) is needed to clarify the optimal dosage and, for long-lived isotopes, the best time for image acquisition after radiotracer administration.…”

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confidence: 99%