Image-guided interventions in the age of theranostics

Alan Matsumoto

“Charles Dotter’s vision transformed the diagnostic catheter into a therapeutic tool and set the foundation for image-guided intervention, and as interventionalists, we have attempted to make the scalpel obsolete by employing technology to treat patients non-operatively. However, today, there is another revolution occurring—theranostics,” said Alan Matsumoto, during his delivery of the Charles J Tegtmeyer Lecture at the International Symposium on Endovascular Therapy (ISET, Hollywood, USA) 2016.

Theranostics, sometimes theragnostics, a term coined in 2002 by the CEO of PharmaNetics, John Funkhouser. seeks to combine a therapeutic drug and diagnostic imaging agent into a single compound that delivers a 1-2 punch to a disease such as cancer. The goal of theranostics is to one day extend the scope of patient care beyond the limits of present day diagnostics and therapeutics, by specif-ically imaging, targeting, treating and monitoring the diseased tissue with a single agent at the molecular and cellular level, while predicting which patient will or will not benefit from the therapy,” noted Matsumoto, professor and chair, Department of Radiology, University of Virginia Health System, Charlottesville, USA.

Matsumoto, the 2015–2016 president of the Society of Interventional Radiology, shed light on how by combining the knowledge of the genetic make-up of the patient with specific cellular pathology and molecular and anatomic-based imaging characteristics, we will be able to create imaging phenotypes that will provide information on which patient sub-population will most likely benefit or have an adverse effect from a treatment. He added, “With the mapping of the human genome, the creation of monoclonal antibodies, nanoparticles and exosomes becoming part of the conversation, and the developments in bioinformatics, proteomics, pharmacogenetics, and molecular and cellular biology, medical imaging and image-guided therapies will be essential for the advancement of theranostic and precision medicine initiatives.”

“Theranostics is moving medical care away from decisions based on large populations of patients to one in which treatment is based on data from smaller, sub-populations; a paradigm shift to more precision in our care,” explained Matsumoto. Indeed, the Precision Medicine Initiative was launched by President Obama during his January 20, 2015 State of the Union Address to “bring us closer to curing diseases like cancer and diabetes – and to give all of us access to the personalised information we need to keep ourselves and our families healthier.” President Obama did include US$215 million in the 2016 budget specifically for precision medicine initiatives. Precision medicine is the term that is preferred over personalised medicine because the focus is at the level of subpopulations, not individuals, noted Matsumoto.

Iodine 131, a nuclear medicine agent that not only images, but also treats, thyroid cancer is an example of a theranostic agent that dates back to the 1940s. A more contemporary theranostic agent is the prostate-specific membrane antigen inhibitor, PSMA-617, that targets a cell surface protein on prostate cancer cells. When PSMA-617 is radiolabeled with gallium-68 (a diagnostic imaging agent) and lutetium-177 (a therapeutic agent), it becomes both a very specific diagnostic and therapeutic agent, and follow-up studies using this agent on patients with prostate cancer reveal a very positive response to therapy,” said Matsumoto.

Matsumoto outlined the challenges facing theranostics and precision medicine: intellectual property and patents; the acquisition and analysis of large volumes of data; and privacy and issues surrounding the use of DNA profiles. “Other big questions that remain will be how the US FDA will oversee and manage approval theranostic agents and if and how the Centers for Medicare and Medicaid Services will reimburse for these services,” he commented.

“Can we afford this type of medicine? The belief and hope is that by eliminating unnecessary or inef-fective therapies, being more precise and targeted with our diagnostic testing and delivery of thera-pies and reducing adverse effects, outcomes will be markedly improved and significant costs will be saved, making theranostics and precision medicine affordable,” he concluded.