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PET-Based Molecular Imaging in Personalized Oncology

01/20/2017


Antonia Dimitrakopoulou-Strauss M.D. is Professor of Nuclear Medicine at the German Cancer Research Center. She was the guest speaker at a lecture organized by the MGH Gordon Center. Below is the presentation summary.

Molecular imaging techniques allow a better staging as well as an individualization and optimization of therapy in oncological patients. The availability of new hybrid scanners, like PET-CT and PET-MRI have revolutionized both diagnosis and therapy management and are therefore a unique tool for personalized cancer treatment. Identification of non-responders early in the course of treatment, the choice of the appropriate therapeutic protocol as well as optimal treatment duration are some aspects which can be improved by the use of molecular imaging techniques and can help to avoid side effects and save costs for the health system. Furthermore, therapies with new targeted drugs, like tyrosine kinase inhibitors or immune checkpoint inhibitors require also a tight monitoring for assessment of a therapeutic result and a fast change to another protocol in case of progress. Standardization of response criteria is another important aspect and a prerequisite for a more routine application of molecular imaging for therapy guidance. Furthermore, the development of new tumor-specific tracers will enable a more accurate assessment of a therapeutic result. Numerous peptides targeting receptoractive tumors are in development with a high potential in a large spectrum of tumors for theranostic approaches, like in neuroendocrine tumors and in prostate cancer.

Dr. Dimitrakopoulou-Strauss delivering her presentation at the MGH Gordon Center

Personalization of Nanotherapeutics Delivery

01/13/2017


Dr. Anne van de Ven is a Research Assistant Professor at Northeastern University. She was the guest speaker at a lecture organized by the MGH Gordon Center. Below is the presentation summary.

Intravital microscopy allows the visualization of nanoparticle transport across a sequence of multi-scale physical barriers. Data collected using this approach can be used to simulate, predict, and improve nanoparticle designs for drug and contrast agent delivery to solid tumors. Dr. van de Ven presented an integrated framework that combines patient-derived xenografts, exogenous contrast agents, and experimental nanoparticles to study how patient-specific transport parameters can impact nanotherapeutics delivery.

According to Dr. van de Ven, preliminary data suggests that only a subset of patients will be highly amenable to nanotherapy. Using ferumoxytol as a surrogate, she is currently developing MRI techniques to quantify nanoparticle delivery and relate it to therapeutic efficacy in vivo for the personalized selection of therapy.

Dr. Anne van de Ven delivering her presentation at the MGH Gordon Center

Post-Translational Modifications and Age-Related Diseases

01/06/2017


Dr. Tae Ho Lee is Assistant Professor of Medicine at Harvard Medical School. He was the guest speaker at a lecture organized by the MGH Gordon Center. Below is his presentation summary.

Dr. Tae Ho Lee delivering his presentation at the MGH Gordon Center

Phosphorylation of proteins is one of the most important post-translational modifications (PTMs) and a key signaling mechanism in diverse physiological and pathological processes. Its deregulation contributes to age-related diseases, notably cancer and Alzheimer’s disease (AD).

AD is characterized by a progressive loss of memory and other cognitive functions. It affects over 44 million people in worldwide and its incidence is expected to triple over the next 30.years. There is therefore an urgent need to understand the mechanisms underlying the degeneration of neuronal cells. The two defining neuropathological features of AD are extracellular senile plaques and intracellular neurofibrillary tangles (NFTs). The senile plaques are made of amyloid-β (Aβ), cleaved products of the amyloid precursor protein (APP), whereas the neurofibrillary tangles mainly consist of the microtubule-associated protein tau. Many hypotheses have been proposed to explain the etiology and pathogenesis of AD and related disorders; two dominant theories focus on increased production of Aβ and dysfunction of tau. However, currently the pathogenic mechanisms are still not fully understood and there is no effective therapy. Therefore, the ability to define regulatory mechanisms controlling APP processing and tau function will be critical for elucidating the pathogenesis and for designing strategies for preventing and/or treating neurodegenerative diseases.

Death-associated protein kinase 1 (DAPK1) is a death domain-containing calcium/ calmodulinregulated serine/threonine kinase and plays an important role in regulating neuronal function. We demonstrated here that DAPK1 expression is dramatically up-regulated in the 75% hippocampi of AD patients compared with age-matched normal subjects. Moreover, we showed that DAPK1 regulates tau toxicity in modulating microtubule assembly and neuronal differentiation, and DAPK1 overexpression increases tau phosphorylation at multiple AD-related sites in cells and animal models. We also found that DAPK1 increases Aβ secretion in a kinase activity-dependent manner. In addition, the levels of insoluble Aβ and amyloidogenic APP processing are significantly reduced in APP-overexpression/DAPK1-knockout mice brain. Finally, we identified novel DAPK1 substrates that are involved in neuronal cell death and AD including N-myc downstream-regulated gene 2 (NDRG2). Together, these results suggest that DAPK1 may be a critical regulator of tau phosphorylation, APP processing, and neuronal cell death and DAPK1 deregulation may contribute to AD progression. Therefore, DAPK1 may serve a potential therapeutic target for AD.

Annual Holiday Party


Thank you to everyone who made it out to our annual holiday party. Take a look at the gallery below for some of the highlights of the evening.

Happy Holidays

12/22/2016


For the upcoming holidays, we will be closed Monday, December 26, and Monday, January 2. We wish you a healthy and happy holiday season!

Happy Holidays & Best Wishes for the New Year

Bradley-Alavi Student Fellowship

12/21/2016


Nicolas Guehl was awarded the SNMMI Bradley-Alavi Student Fellowship based on his proposal “Development of methods for simultaneous rest-stress myocardial blood flow (MBF) measurements.” The fellowship is funded by the Education and Research Foundation for Nuclear Medicine and Molecular Imaging and is designed to support research activities in nuclear medicine and molecular imaging for three months. Nicolas Guehl is a research fellow at the MGH Gordon Center.

Nicolas Guehl

Neuroplastic Changes in Blind Individuals

12/20/2016


 

This article was initially published by the RSNA Daily Bulletin on November 30, 2016.

Dr. Laura Ortiz-Terán is a clinical radiologist and neuroimaging research scientist at the MGH Gordon Center. She works with Dr. Jorge Sepulcre to investigate the neuroplastic changes occurring in blind individuals, adults and children, using graph theory based resting-state functional connectivity analysis.

Novel Radioligand for Brain Imaging

12/16/2016


Central nervous system demyelination represents the pathological hallmark of multiple sclerosis (MS) and is thought to contribute to other neurological conditions including traumatic brain injury, stroke and Alzheimer’s disease. The ability to assess demyelination quickly and quantitatively is crucial for the diagnosis and treatment of these diseases. As current imaging approaches for demyelination rely on magnetic resonance imaging, which is neither quantitative nor specific for demyelination, Dr. Pedro Brugarolas set out to develop a PET tracer for demyelination. He described the development of a novel radioligand for brain imaging based on the FDA-approved drug for MS, 4-aminopyridine (4-AP). After demonstrating that C-14 labeled 4-AP localizes to demyelinated areas in mouse models of MS –presumably through binding to exposed potassium channels in demyelinated axons– he designed a fluorinated derivative of 4-AP compatible with with F-18 labeling and PET. Dr. Brugarolas then developed a novel radiochemical method to label this compound and performed PET/CT imaging in rats harboring demyelinated lesions. According to Dr. Pedro Brugarolas, this is the first example of a PET radioligand for potassium channels in the brain potentially opening a new window for looking at brain diseases.

Dr. Pedro Brugarolas is a radiochemist at the University of Chicago. He was the guest speaker of a lecture organized by the Gordon Center and his presentation was titled "[18F]3F4AP: a new PET tracer for imaging brain demyelination."

Pedro Brugarolas, Ph.D.
Department of Neurology
The University of Chicago