Radioimmunotherapy of Human Breast Cancer Xenografts Using 131i/Icr12 Against C-Erb B2 Labelled Using Iodogen and N-Succinimidyl 3-(Tri-N-Butylstannyl) Benzoate

Smellie, W. J. B.; Eccles, Sue; Carnochan, P.; Zalutzky, M. R.; Garg, Pankaj; Dean, Christopher; Sacks, N. P. M.

doi:10.1097/00002371-199408000-00047

Cited by 6 publications

(7 citation statements)

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“…Tumor uptake of ICR12 was further increased, to 20 %ID/g, with residualizing isotopes (28,29). Similar to what we observed in the present study, tumor uptake of ICR12 was not influenced by the protein dose, but the T/B ratio decreased with an increasing amount of protein (30). With the murine predecessor of trastuzumab (4D5), maximal tumor uptake was 35% (31,32), comparable to what we found.…”

Section: Discussionsupporting

confidence: 91%

Development and Characterization of Clinical-Grade ⁸⁹Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

Dijkers¹,

Kosterink²,

Rademaker³

et al. 2009

J Nucl Med

313

256

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The anti-human epidermal growth factor receptor 2 (HER2/neu) antibody trastuzumab is administered to patients with HER2/ neu-overexpressing breast cancer. Whole-body noninvasive HER2/neu scintigraphy could help to assess and quantify the HER2/neu expression of all lesions, including nonaccessible metastases. The aims of this study were to develop clinical-grade radiolabeled trastuzumab for clinical HER2/neu immunoPET scintigraphy, to improve diagnostic imaging, to guide antibodybased therapy, and to support early antibody development. The PET radiopharmaceutical 89 Zr-trastuzumab was compared with the SPECT tracer 111 In-trastuzumab, which we have tested in the clinic already. Methods: Trastuzumab was labeled with 89 Zr and (for comparison) with 111 In. The minimal dose of trastuzumab required for optimal small-animal PET imaging and biodistribution was determined with human HER2/neu-positive or -negative tumor xenograft-bearing mice. Results: Trastuzumab was efficiently radiolabeled with 89 Zr at a high radiochemical purity and specific activity. The antigen-binding capacity was preserved, and the radiopharmaceutical proved to be stable for up to 7 d in solvent and human serum. Of the tested protein doses, the minimal dose of trastuzumab (100 mg) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of 89 Zr-trastuzumab in HER2/neu-positive tumors than in HER2/neu-negative tumors, especially at day 6 (33.4 6 7.6 [mean 6 SEM] vs. 7.1 6 0.7 percentage injected dose per gram of tissue). There were good correlations between the small-animal PET images and the biodistribution data and between 89 In-trastuzumab uptake in tumors (R 2 5 0.972). Conclusion: Clinical-grade 89 Zr-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution.

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Section: Discussionsupporting

confidence: 91%

Development and Characterization of Clinical-Grade ⁸⁹Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

Dijkers¹,

Kosterink²,

Rademaker³

et al. 2009

J Nucl Med

313

256

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“…In the upper aerodigestive tract overexpression of HER2/neu has been reported in 15-25% of head and neck carcinomas , with the possible exception of laryngeal carcinomas [224,225]. Interestingly, in head and neck squamous cell carcinoma <7% of patients had membrane staining of HER2/neu [207].…”

Section: Head and Neckmentioning

confidence: 99%

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

Nelson¹

2014

Clinical Investigation

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No biological molecule in the field of oncology has been more extensively or more successfully targeted for therapeutic intent than the product of the c-erbB2 gene, HER2/neu. This is the second of a comprehensive three-part review of the foundation for and therapeutic targeting of HER2/neu. The distribution of HER2/neu overexpression and/or gene amplification by individual tumor sites and histologies will be comprehensively surveyed and described. This provides a bridge between the primarily basic science focused Part I, and the survey of clinical applications to follow in Part III. In combination, this comprehensive survey will identify opportunities and promising areas for future evaluation of HER2/neu-targeted therapies, highlighting the importance of HER2/neu as an increasingly important therapeutic target.

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“…Monoclonal antibody ICR12 is a rat IgG 2a with high affinity for an external epitope on the protein core of HER-2 (33,34). RIT with 131 I labeled ICR12 in athymic mice bearing MDA-MB-361 human breast cancer xenografts showed growth inhibition for >24 days at a dose of 600 µCi/mouse (33,35). A 99m Tc labeled ICR12 had 20 % ID/g tumor uptake, four times greater than that in normal tissues, based on biodistribution study in a mouse model system.…”

Section: Murine Monoclonal Antibodiesmentioning

confidence: 99%

Molecular imaging of human epidermal growth factor receptor 2 (HER-2) expression

Niu¹

2008

Front Biosci

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The human epidermal growth factor receptor 2 (HER-2) is a key member of the HER family of receptor tyrosine kinases. Activation of HER-2 affects cell growth, proliferation, migration, adhesion, and survival. Due to its crucial role in carcinogenesis and tumor progression, HER-2 has been intensively investigated as a target for cancer therapy. The ability to quantitatively image HER-2 expression in a noninvasive manner can aid in lesion detection, patient stratification, new drug development/validation, dose optimization, and treatment monitoring. This review summarizes the current state of understanding in multimodality imaging of HER-2 using positron emission tomography (PET), single photon emission computed tomography (SPECT), optical, and magnetic resonance (MR) imaging with HER-2 specific antibodies, antibody derivatives and affibodies as targeting ligands. Successful development of new HER-2 targeted imaging agents with optimal in vivo stability, targeting efficacy, and desirable pharmacokinetics for clinical translation will enable maximum benefit in cancer patient management.

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Radioimmunotherapy of Human Breast Cancer Xenografts Using 131i/Icr12 Against C-Erb B2 Labelled Using Iodogen and N-Succinimidyl 3-(Tri-N-Butylstannyl) Benzoate

Cited by 6 publications

References 0 publications

Development and Characterization of Clinical-Grade ⁸⁹Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

Development and Characterization of Clinical-Grade ⁸⁹Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

Molecular imaging of human epidermal growth factor receptor 2 (HER-2) expression

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Radioimmunotherapy of Human Breast Cancer Xenografts Using 131i/Icr12 Against C-Erb B2 Labelled Using Iodogen and N-Succinimidyl 3-(Tri-N-Butylstannyl) Benzoate

Cited by 6 publications

References 0 publications

Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

Molecular imaging of human epidermal growth factor receptor 2 (HER-2) expression

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Product

Resources

About

Development and Characterization of Clinical-Grade ⁸⁹Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

Development and Characterization of Clinical-Grade ⁸⁹Zr-Trastuzumab for HER2/neu ImmunoPET Imaging