Imaging of HER2 with [<sup>89</sup>Zr]pertuzumab in Response to T-DM1 Therapy

Massicano, Adriana V F; Lee, Supum; Crenshaw, Bryant K; Aweda, Tolulope; Sayed, Retta El; Super, Ian; Bose, Ron; Marquez-Nostra, Bernadette; Lapi, Suzanne E.

doi:10.1089/cbr.2018.2654

Cited by 24 publications

(26 citation statements)

References 33 publications

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“…We have recently shown that high HER2 expression is associated with aggressive disease and poor survival in EC [41]. 89 Zr-labeled pertuzumab ( 89 Zr-pertuzumab) has been used to detect HER2-positive breast cancer in small human cohorts [42,43] and to delineate tumors and show treatment effects from trastuzumab-emtansine (T-DM1) in HER2-positive breast cancer xenografts [44]. Similarly, PET-CT with radiolabeled pertuzumab ( 64 Cu-NOTA-pertuzumab) was used for non-invasive detection and monitoring of HER2 tumor expression, enabling the detection of primary tumors and peritoneal metastases in both subcutaneous and orthotopic models of ovarian cancer [45].…”

Section: Radioligands For Visualization Of Target-specific Expressionmentioning

confidence: 99%

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Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Espedal

Fonnes

Fasmer

et al. 2019

Cancers

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Endometrial cancer is the most common gynecologic malignancy in industrialized countries. Most patients are cured by surgery; however, about 15% of the patients develop recurrence with limited treatment options. Patient-derived tumor xenograft (PDX) mouse models represent useful tools for preclinical evaluation of new therapies and biomarker identification. Preclinical imaging by magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), single-photon emission computed tomography (SPECT) and optical imaging during disease progression enables visualization and quantification of functional tumor characteristics, which may serve as imaging biomarkers guiding targeted therapies. A critical question, however, is whether the in vivo model systems mimic the disease setting in patients to such an extent that the imaging biomarkers may be translatable to the clinic. The primary objective of this review is to give an overview of current and novel preclinical imaging methods relevant for endometrial cancer animal models. Furthermore, we highlight how these advanced imaging methods depict pathogenic mechanisms important for tumor progression that represent potential targets for treatment in endometrial cancer.

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Section: Radioligands For Visualization Of Target-specific Expressionmentioning

confidence: 99%

“…xenografts (BT-474) including evaluation of tumor size change after treatment with HER2-targeted antibody-drug conjugate (T-DM1) [44]. 64 Cu-NOTA-pertuzumab…”

Section: Radioligands For Visualization Of Target-specific Expressionmentioning

confidence: 99%

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Espedal

Fonnes

Fasmer

et al. 2019

Cancers

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“… 10 Currently in phase II clinical trials, the 89 Zr radiolabeled antibody is injected and requires a 4-7 day post-injection imaging time. 10 , 11 The long imaging time points, due to the circulation time of the antibody, can create logistic challenges for both patients and facilities. To pair with the biological half-life and optimal scanning time for the antibodies, longer-lived isotopes must be used which increases the amount of radiation exposure to both the patients and the personnel involved in the synthesis of the radiopharmaceuticals.…”

Section: Introductionmentioning

confidence: 99%

Peptide Based Imaging Agents for HER2 Imaging in Oncology

Ducharme

Lapi

2020

Mol Imaging

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Breast cancer continues to be the most lethal cancer type in women and one of the most diagnosed. Understanding Breast cancer receptor status is one of the most vital processes for determining treatment options. One type of breast cancer, human epidermal growth factor receptor 2 (HER2) positive, has approved receptor-based therapies including trastuzumab and pertuzumab that can significantly increase the likelihood of survival. Current methods to determine HER2 status include biopsies with immunohistochemical staining and/or fluorescence in situ hybridization. However, positron emission tomography (PET) imaging techniques using 89Zr-trastuzumab or 89Zr-pertuzumab are currently in clinical trials for a non-invasive, full body diagnostic approach. Although the antibodies have strong specificity to the HER2 positive lesions, challenges involving long post-injection time for imaging due to the blood circulation of the antibodies and matching of long-live isotopes leading to increased dose to the patient leave opportunities for alternative PET imaging probes. Peptides have been shown to allow for shorter injection-to-imaging time and can be used with shorter lived isotopes. HER2 specific peptides under development will help improve the diagnosis and potentially therapy options for HER2 positive breast cancer. Peptides showing specificity for HER2 could start widespread development of molecular imaging techniques for HER2 positive cancers.

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“…However, the invasive method may not be reliable because the HER2 expression is heterogeneous in the tumors and varies during the progress of the disease [9]. Almost 20% of the outcomes was inaccurate [10].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a novel 89Zr-labeled HER2 affibody and its application study in tumor PET imaging

Wang

Pan

et al. 2020

EJNMMI Res

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Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues, etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89 Zr-labeled HER2 affibody, [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2 was 90.2 ± 1.9%, and the radiochemical purity was higher than 95%. The total synthesis time was only 30 min. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe was highly retained in SKOV-3 xenografts even for 48 h. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5% IA/g during 48 h postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels (~1% IA/g). The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.

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Imaging of HER2 with [⁸⁹Zr]pertuzumab in Response to T-DM1 Therapy

Cited by 24 publications

References 33 publications

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Peptide Based Imaging Agents for HER2 Imaging in Oncology

Synthesis of a novel 89Zr-labeled HER2 affibody and its application study in tumor PET imaging

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Imaging of HER2 with [89Zr]pertuzumab in Response to T-DM1 Therapy

Cited by 24 publications

References 33 publications

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Peptide Based Imaging Agents for HER2 Imaging in Oncology

Synthesis of a novel 89Zr-labeled HER2 affibody and its application study in tumor PET imaging

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Product

Resources

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Imaging of HER2 with [⁸⁹Zr]pertuzumab in Response to T-DM1 Therapy