Evaluation of [89Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer

Dehdashti, Farrokh; Wu, Ningying; Bose, Ron; Naughton, Michael; Cynthia, X.; Marquez-Nostra, Bernadette; Diebolder, Philipp; Mpoy, Cedric; Rogers, Buck E.; Lapi, Suzanne E.; Laforest, Richard; Siegel, Barry A.

doi:10.1007/s10549-018-4696-z

Cited by 68 publications

(52 citation statements)

References 16 publications

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“…89 Zr ( T 1/2 = 3.27 d) has been emerging as a well‐suited nuclide for the imaging of intact antibodies and nanoparticles. Many studies have illustrated the utility of 89 Zr‐labelled agents for PET imaging in both preclinical and clinical research studies …”

Section: Radiometals For Theranostic Applicationsmentioning

confidence: 99%

Radiometals for imaging and theranostics, current production, and future perspectives

Mikołajczak

Meulen

Lapi

2019

Labelled Comp Radiopharmac

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The aim of this review is to make the reader familiar with currently available radiometals, their production modes, capacities, and quality concerns related to their medical use, as well as new emerging radiometals and irradiation technologies from the perspective of their diagnostic and theranostic applications. Production methods of 177Lu serve as an example of various issues related to the production yield, specific activity, radionuclidic and chemical purity, and production economy. Other radiometals that are currently used or explored for potential medical applications, with particular focus on their theranostic value, are discussed. Using radiometals for diagnostic imaging and therapy is on the rise. The high demand for radiometals for medical use prompts investigations towards using alternative irradiation reactions, while using existing nuclear reactors and accelerator facilities. This review discusses these production capacities and what is necessary to cover the growing demand for theranostic nuclides.

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Section: Radiometals For Theranostic Applicationsmentioning

confidence: 99%

Radiometals for imaging and theranostics, current production, and future perspectives

Mikołajczak

Meulen

Lapi

2019

Labelled Comp Radiopharmac

Self Cite

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“…[16][17][18] For example, 89 Zr-trastuzumab PET/CT detected unsuspected HER2-positive metastases in patients with HER2-negative primary breast cancer. [19] It also found lesions in patients with metastatic HER2-positive esophagogastric cancer [20] . However, the optimal images with favorable contrasts should be acquired several days (3-5days) after administration of the antibodies because of large molecular size (150 kDa), slow tumor penetration and long half-life in circulation.…”

Section: Introductionmentioning

confidence: 95%

“…However, the optimal images with favorable contrasts should be acquired several days (3-5days) after administration of the antibodies because of large molecular size (150 kDa), slow tumor penetration and long half-life in circulation. [19] Affibody, an engineered small protein (~7 KDa) that originated from the IgG-binding staphylococcal protein A, is an alternative ligand towards HER2. It is an ideal compound for recognizing the desired targets due to ease of chemical synthesis, quick tumor accumulation and rapid blood clearance, etc.…”

Section: Introductionmentioning

confidence: 99%

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

Xu¹,

Wang²,

Pan³

et al. 2020

Preprint

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Background: Human epidermal growth factor receptor-2 (HER2) is an important biomarker for tumor diagnosis and therapy. Affibody is an ideal vector for preparing HER2 specific probes due to the advantages such as high affinity and rapid blood clearance etc. 89Zr is a novel PET imaging isotope with long half-lives and suitable for tracking biological processes for longer periods. In this study, a novel 89Zr labeled HER2 affibody, 89Zr-DFO-MAL-Cys-MZHER2, was synthesized and its imaging properties were also evaluated. Results: The precursors, DFO-MAL-Cys-MZHER2, were obtained with the yields of nearly 50%. The yields of 89Zr -DFO-MAL-Cys-MZHER2 were 90.2±1.9% and the radiopurities were more than 95%. The total synthesis time was only 30 minutes. The probes were stable in PBS and serum. The tracer accumulated in HER2 overexpression human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissue. ROI analysis revealed that the average uptakes in the tumor were greater than 5 %ID/g. On the contrary, the counterparts of MCF-7 tumors kept low levels of （~1%ID/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the blood and normal organs, 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. 89Zr-DFO-MAL-MZHER is a potential candidate for monitoring HER2 expression and may play specific roles in clinical cancer theranostics.

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Section: Introductionmentioning

confidence: 95%

“…However, the optimal images with favorable contrasts should be acquired several days (3-5days) after the administration of the antibodies. [19] A body, an engineered small protein that originated from the IgG-binding staphylococcal protein A, is an alternative ligand towards HER2. It is an ideal compound for recognizing the desired targets due to ease of chemical synthesis, quick tumor accumulation and rapid blood clearance, etc.…”

Section: Introductionmentioning

confidence: 99%

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

Xu¹,

Wang²,

Pan³

et al. 2020

Preprint

View full text Add to dashboard Cite

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 89Zr-labeled HER2 affibody, [89Zr]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 [89Zr]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 minutes. 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 highly retained in SKOV-3 xenografts even for 48 hours. 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 hours 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. [89Zr]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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Evaluation of [89Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer

Abstract: [Zr]trastuzumab has the potential to characterize the HER2 status of the complete tumor burden in patients with breast cancer, thus obviating repeat or multiple tissue sampling to assess intrapatient heterogeneity of HER2 status.

Cited by 68 publications

References 16 publications

Radiometals for imaging and theranostics, current production, and future perspectives

Radiometals for imaging and theranostics, current production, and future perspectives

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

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

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