89Zr-trastuzumab PET for Imaging the Effect of HSP90 Inhibition

2014-07-23 21:09:55 | BioPortfolio


HSP90 inhibition is a potentially new targeted drug modality in the treatment of HER2 positive, trastuzumab refractory breast cancer. Little is known about the pharmacodynamics of HSP90 inhibitors in vivo, but non-invasive PET/CT imaging in a xenograft mouse model could visualize and quantify HER2 reduction after AUY922 treatment by 89Zr-trastuzumab PET imaging. Two doses of 50 mg/kg AUY922 resulted in a decrease in HER2 expression of approximately 50%, quantified 6 days after the last administration of AUY922.

Visualizing HER2 expression in breast cancer patients before and early following HSP90 inhibition by means of 89Zr-trastuzumab PET, is likely to provide insight in the early in vivo effect of HSP90 inhibition and could potentially support patient tailored therapy.


This study is designed as a side study to the multicenter, international phase I-II trial with the HSP90 inhibitor AUY922 (protocol CAUY922A2101), as part of the biomarker assessment. In protocol CAUY922A2101, section 4, the design of this phase I-II trial is described (p36, 37). Briefly, a dose-escalation study is performed according to phase I design. This part is followed by a dose-expansion study according to a phase II design. In the latter part, breast cancer patients are enrolled that are either refractory to hormone- or trastuzumab treatment (both treatment arms, n=40 patients). Patients with HER2 positive, trastuzumab refractory breast cancer, will receive a 89Zr-trastuzumab PET scan as part of the present side study protocol, which will be performed in collaboration with the Royal Marsden Hospital (United Kingdom).

To this end, a 89Zr-trastuzumab PET scan will be performed before (baseline) and during treatment with the HSP90 inhibitor AUY922, as described below.

A minimum of six patients are needed to evaluate whether the 89Zr-trastuzumab PET scan can be used for the detection of a decrease of HER2 expression, induced by HSP90 inhibition.

Study Design

Observational Model: Cohort, Time Perspective: Prospective


Breast Cancer


Imaging with 89Zr-trastuzumab PET


University Medical Center Groningen
9713 GZ




University Medical Centre Groningen

Results (where available)

View Results


Published on BioPortfolio: 2014-07-23T21:09:55-0400

Clinical Trials [5220 Associated Clinical Trials listed on BioPortfolio]

PET Imaging With 89Zr-Trastuzumab for Prediction of HER2 Targeted Therapy Effectiveness

Our goal is to investigate the use of 89Zr-trastuzumab as a HER2 imaging agent to determine which patients are likely to respond to targeted HER2 agents as single agent therapy. We are pro...

89Zr-girentuximab ) Dosimetry in CCRC Study - ZIR-DOSE

The study is designed to explore the safety and tolerability as well as diagnostic 89Zr-girentuximab for imaging CCRC by PET/CT. This study does not offer any treatment for patients with C...

89Zr-MMOT PET Imaging in Pancreatic and Ovarian Cancer Patients

The purpose of this multicenter imaging sub study is to evaluate the biodistribution and organ pharmacokinetics of 89Zr-MMOT0530A in patients with unresectable pancreatic or platinum-resis...

HER2 Imaging Study to Identify HER2 Positive Metastatic Breast Cancer Patient Unlikely to Benefit From T-DM1

T-DM1 , which is a highly innovative but also expensive antiHER2 agent consisting in the coupling of the humanised monoclonal antibody trastuzumab with a cytotoxic agent (maytansine deriva...

The Use of FES-PET Imaging as a Tool to Detect a Possible Reversion of Estrogen Receptor (ER)-α Status in Patients With Metastatic Breast Cancer HER2 + and ERα Neg Treated With Trastuzumab + Pertuzumab + Taxane.

This is an exploratory, prospective and multicentric study aiming to highlight by FES-PET imaging that an anti-HER2 treatment by trastuzumab + pertuzumab can reverse the ERα status in pat...

PubMed Articles [19559 Associated PubMed Articles listed on BioPortfolio]

Positron-Emission Tomography (PET) of HER2-Positive Breast Cancer Xenografts in Mice with 89Zr-Labeled Trastuzumab-DM1 (T-DM1) - Comparison with 89Zr-Labeled Trastuzumab.

Our aim was to synthesize 89Zr-labeled trastuzumab-emtansine (89Zr-DFO-T-DM1) to probe the delivery of trastuzumab-emtansine (T-DM1) to HER2-positive breast cancer (BC) by positron emission tomography...

LMO4 mediates trastuzumab resistance in HER2 positive breast cancer cells.

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Trastuzumab (Herceptin) is an effective antibody drug for HER2 positive breast cancer; or acquired trastuzumab resis...

A randomized phase II trial of trastuzumab plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes: WJOG6110B/ELTOP.

For human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to la...

Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for patients with early HER2-positive primary breast cancer: a network meta-analysis.

Trastuzumab (H) with chemotherapy benefits patients with HER2+ breast cancer (BC); however, we lack head-to-head pairwise assessment of survival or cardiotoxicity for specific combinations. We sought ...

One year versus a shorter duration of adjuvant trastuzumab for HER2-positive early breast cancer: a systematic review and meta-analysis.

One year is the standard duration of adjuvant trastuzumab for human epidermal receptor-2 (HER2) positive (HER2+) breast cancer (BC). Indeed, a shorter duration of trastuzumab can reduce cardiotoxicity...

Medical and Biotech [MESH] Definitions

A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed.

Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical or radiation breast cancer treatments (e.g., MASTECTOMY).

Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.

Use of ultrasound for imaging the breast. The most frequent application is the diagnosis of neoplasms of the female breast.

A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)

More From BioPortfolio on "89Zr-trastuzumab PET for Imaging the Effect of HSP90 Inhibition"

Quick Search


Relevant Topic

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Searches Linking to this Trial