A 2-Helix Small Protein Labeled with 68Ga for PET Imaging of HER2 Expression

11572 Background: 18F-Fluoroestradiol (FES) is an estrogen analogue that has been shown to be a promising biomarker in ER imaging of breast cancer. FES uptake correlates to ER expression, provides qualitative and quantitative assessment of multiple tumor sites simultaneously, and can predict response to endocrine therapies. Tumor heterogeneity is a known feature of metastatic breast cancer. Our work and others has shown that patients that have tumors with high FDG-PET SUV and low FES-PET SUV uptake have a poorer prognosis. Biopsies of metastatic disease may be done initially for diagnosis of metastatic disease, but are generally only performed in the setting of target identification for clinical trials. A change in ER or HER2 expression, however, can result in a change in therapy. FES-PET imaging offers a virtual biopsy and can reveal heterogeneity of the entire tumor burden. Methods: We reviewed our prior evaluations of tumor heterogeneity with FES-PET from 3 different studies. 46 breast cancer patients with metastatic disease (de novo or recurrent) who had biopsy proven ER+ primary breast cancer underwent FES-PET and FDG-PET imaging and a biopsy of a metastatic lesion prior to therapy initiation. ER and HER-2 expression was reviewed. Results: Of the 46 patients, 5 (11%) had ER- metastatic biopsies. One (2%) biopsy changed from ER+/HER-2 neg to ER-/HER-2+, and one (2%) biopsy changed from ER+/HER-2+ to ER+/HER-2-. All 5 patients (11%) with changes in ER/HER2 expression underwent a change in therapy due to the unexpected findings by metastatic biopsy. FDG findings helped to guide selection of biopsy sites. FES quantitative measures correlated with biopsy findings. Conclusions: Biopsy resulted in a change in therapy for > 10 % of patients enrolled in trials of FES imaging. Imaging can help identify heterogeneous tumor locations to assist identification of evolving tumor targets in breast cancer. In addition, FES imaging may reveal a change in tumor phenotype that can ultimately affect choice of therapy. Research Support: P01CA42045, R01CA72064

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[89Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models

Molecules ◽

10.3390/molecules26061568 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1568

Author(s):

Yun Lu ◽

Meng Li ◽

Adriana V. F. Massicano ◽

Patrick N. Song ◽

Ameer Mansur ◽

...

Keyword(s):

Breast Cancer ◽

Mouse Models ◽

Pet Imaging ◽

Treatment Efficacy ◽

Human Breast Cancer ◽

Expression Level ◽

Her2 Expression ◽

Human Breast ◽

Pet Ct ◽

18F Fdg

Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [89Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [18F]-fluorodeoxyglucose ([18F]-FDG) PET/CT imaging. Spearman’s correlation, Kendall’s tau, Kolmogorov–Smirnov test, and ANOVA were used for statistical analysis. [89Zr]-pertuzumab mean standard uptake values (SUVmean) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2−) tumors were 1.1 ± 0.4. [18F]-FDG SUVmean changes were negatively correlated with [89Zr]-pertuzumab SUVmean (r = −0.5887, p = 0.0030). The baseline [18F]-FDG SUVmean was negatively correlated with initial [89Zr]-pertuzumab SUVmean (r = −0.6852, p = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.

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64Cu-DOTA-trastuzumab-PET imaging in patients with HER2-positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10519 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10519-10519 ◽

Cited By ~ 3

Author(s):

Kenji Tamura ◽

Hiroaki Kurihara ◽

Kan Yonemori ◽

Kazuhiro Takahashi ◽

Yasuhiro Wada ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Radiation Exposure ◽

Pet Imaging ◽

Half Life ◽

Normal Tissue ◽

Her2 Expression ◽

Her2 Positive ◽

Resolution Image ◽

Positive Breast Cancer

10519 Background: Targeting of HER2 with trastuzumab (T) is a well-established strategy in the metastatic and adjuvant setting in HER2 positive breast cancer (HER2-BC). Although HER2 status is routinely determined using immunohistochemistry or fluorescence in situ hybridization, technical problem can arise when lesions are poorly accessible. HER2 expression can vary during the course of the disease, and there can be discordance in HER2 expression across tumor lesion even in the same patients. Noninvasive HER2 imaging is crucial needed to solve these problems. Previous imaging using 111In or 89Zn- trastuzumab produced high radiation exposure to patients by their long half life (=67.9and 78.4h) and low resolution image. Half life of 64Cu is 12.7h. We performed a feasibility study of the 64Cu-1, 4, 7, 10- tetraazacylododecane-N,N',N",N"'-tetraacetic acid (DOTA)-T to perform PET imaging in patients with HER2-BC. Methods: Patients with HER2-BC received 150 MBq of 64Cu-DOTA-T and underwent PET scan 1, 24 and 48h after the injection. Six patients were evaluated internal dosimetry by collecting radioactivity data of blood and normal tissue in each time point from PET study, and radiation exposure by collecting clothes, linen and urine to test feasibility for outpatients. Results: Fifteen patients who received T therapy were enrolled in the “first-in-human” trial. All patients had no severe toxicity. Radiation excretion evaluating clothes, linen were under background level. Radiation exposure of 64Cu-DOTA-T was equivalent to that of conventional 18F-FDG-PET. Distribution of liver, kidney, spleen, and blood vessel was 2-8 SUV, and uptake in other normal tissue was low. At visual examination, in two patients brain metastases were clearly visualized by 64Cu-DOTA-T-PET, suggesting that there are disruptions of the blood-brain barrier at the site of the brain metastases. The sternum bone metastasis was well visualized and quantitatively monitored according to the response by T. Primary breast cancers, lymph node metastases and lung metastases could also be visualized at the lesion indentified by CT. Conclusions: 64Cu-DOTA-T-PET was feasible test even for outpatient, and provides specific and high resolution image in HER2 positive lesion.

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