News | Nuclear Imaging | September 20, 2016

PET Probe Images Breast Cancer’s Ability to Foil Treatment

Researchers believe the technique could be used to guide further treatment to avoid pathway blocks

PET probes, breast cancer, surface receptor changes, MGH study, Memorial Sloan Kettering

After molecularly targeted therapy with an AKT inhibitor, the receptor tyrosine kinase (RTK) HER3 increases in this particular tumor, but the RTK EGFR does not. In this example, starting HER3 inhibitor therapy in addition to AKT inhibitor therapy is likely to be beneficial, but the addition of EGFR inhibitor therapy is not likely to be beneficial for treating this tumor. Image courtesy of Massachusetts General Hospital, Boston.

September 20, 2016 — Cancer biologists know that inhibitor-mediated feedback loop changes (increased expression of a cell surface receptor in response to target inhibition) can result in breast cancer treatment failure and the need for additional therapy. A recent study by researchers at Massachusetts General Hospital in Boston and at Memorial Sloan Kettering in New York City shows that imaging of these cell surface receptor changes with positron emission tomography (PET) probes specific to epidermal growth factor receptor 1 (EGFR) and human epidermal growth factor receptor 3 (HER3) directly addresses this unmet need in cancer therapy decision-making, while avoiding the need for repeated biopsies. The study is reported in the September issue of The Journal of Nuclear Medicine.

“In some cases, cancer cells can adapt quickly to overcome these pathway blocks by increasing the upstream signaling receptors that help drive these pathways — analogous to cancer cells turning a faucet a few turns to increase the water pressure through a hose to overcome a kink we placed in the hose downstream,” explains Umar Mahmood, M.D., Ph.D., of the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston.

“We can image that upregulation of cell surface signaling receptors and, in fact, can image which specific surface receptors have increased expression after downstream targeted inhibitor therapy is started,” he adds. “This allows the rational addition of a second therapy to block this inhibitor-mediated signaling receptor increase. In a game of chess with the cancer cell, we have made a move by blocking a signaling node. The cancer cell has responded by increasing a cell surface receptor to overcome this block, and our imaging allows us to make an optimal move to specifically block the type of cell surface receptor the cell increased.”

The imaging studies, using newly developed PET probes specific to EGFR and HER3, show that changes in receptor tyrosine kinases (RTK) expression indicative of resistance to phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) inhibitors can be seen within days of therapy initiation, and are of sufficient magnitude to be useful for clinical interpretation as this technology is translated. Noninvasive PET monitoring of these RTK feedback loops should help to rapidly assess resistance to PI3K and AKT inhibitors and guide selection of an appropriate, additional therapeutic regimen for the individual patient.

Authors of the article “Differential Receptor Tyrosine Kinase PET Imaging for Therapeutic Guidance” include Eric Wehrenberg-Klee, N. Selcan Turker, Pedram Heidari, Benjamin Larimer, Dejan Juric, and Umar Mahmood, Massachusetts General Hospital, Boston, Massachusetts; José Baselga and Maurizio Scaltriti, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.

This research was supported by NIH U01CA084301, P50CA127003, and U01CA143056; by a “Stand Up to Cancer” Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACRDT0209) and the Breast Cancer Research Foundation; and by the Dubai Harvard Foundation for Medical Research (DHFMR, grant number 223439).

For more information: www.jnm.snmjournals.org

Related Content

IBA Gathers Experts on Flash Irradiation During ASTRO
News | Proton Therapy | September 17, 2019
IBA (Ion Beam Applications SA, held its third Victoria Consortium Meeting focusing on Flash irradiation at the 2019...
Noninvasive Radioablation Offers Long-term Benefits to High-risk Heart Arrhythmia Patients
News | Radiation Therapy | September 17, 2019
September 17, 2019 — Treating high-risk heart patients with a single, high dose of...
Sun Nuclear Presents Portfolio of Independent Radiotherapy QA Solutions at ASTRO 2019

The PlanCheck module now part of SunCheck, automates plan quality checks, validates treatment plans against requirements, and automatically assesses plan performance versus intent.

News | Quality Assurance (QA) | September 16, 2019
At the 2019 American Society for Radiation Oncology (ASTRO) Annual Meeting, running Sept. 15-18 in Chicago, Sun Nuclear...
Varian Unveils Ethos Solution for Adaptive Radiation Therapy
News | Image Guided Radiation Therapy (IGRT) | September 16, 2019
At the 2019 American Society for Radiation Oncology (ASTRO) annual meeting, being held Sept. 15-18 in Chicago, Varian...
Long-term Hormone Therapy Increases Mortality Risk for Low-PSA Men After Prostate Surgery
News | Prostate Cancer | September 16, 2019
Secondary analysis of a recent clinical trial that changed the standard of care for men with recurring prostate cancer...
The Siemens Somatom Go.Sim computed tomography (CT) system for dedicated radiation therapy planning

The Siemens Somatom Go.Sim computed tomography (CT) system for dedicated radiation therapy planning. Image courtesy of Siemens Healthineers.

News | Computed Tomography (CT) | September 15, 2019
Siemens Healthineers debuted two computed tomography (CT) systems dedicated to radiation therapy (RT) planning at the...
Isoray to Spotlight Cesium-131 Advances at ASTRO Annual Meeting
News | Brachytherapy Systems | September 13, 2019
Isoray Inc. announced it will spotlight the growing cancer treatment applications of Cesium-131 brachytherapy at the...
Akesis Galaxy SRS System Receives FDA 510(k) Clearance
Technology | Radiation Therapy | September 13, 2019
The Akesis Galaxy, a gamma stereotactic radiosurgery system (SRS) with continuous 360-degree rotational technology, has...
Philips Showcases Integrated Radiation Oncology Portfolio at ASTRO 2019
News | Radiation Oncology | September 13, 2019
Philips will showcase its integrated radiation oncology portfolio at the American Society of Radiation Oncology (ASTRO...
RefleXion Highlights Novel Approach to Radiotherapy at ASTRO 2019

The RefleXion X1 Machine without the Gantry Cover. The patented technology incorporates PET imaging data, which enables tumors to continuously signal their location. Image courtesy of Reflexion Medical.

News | Radiation Therapy | September 12, 2019
Therapeutic oncology company RefleXion Medical announced it will showcase the RefleXion X1 Machine at the American...