Theranostics: an old approach with new interest
Introduction
Precision medicine has been a growing trend in healthcare for years. Doctors and researchers are leveraging computer power, modern analytics, cloud technology and patient information from genomics to demographics to help make more individualized and accurate treatment plans. What if there were a more direct link between a diagnostic test and the potential therapies available for a patient? Well that is the aim of theranostics, a field of personalized and precision medicine that links targeted therapies to specific diagnostic tests. Theranostics represents one approach for transitioning from conventional medicine to a more contemporary patient-specific analysis and therapy (1). While having evolved into a number of particular approaches, a theme currently in vogue is the use of either micro- or nano-particles in a marriage of diagnostic imaging and therapeutic activities. This results in the use of a single nano-particle agent to be employed in screening, diagnosis and treatment delivery as well as in prognosis or response monitoring.
Theranostics
Theranostics relies upon the very same specific biological pathways and chemistries to drive both the diagnostic potential, as well as to deliver or effect the identified therapy in the patient. For example, the surface of a gold
nanoparticle with a therapeutic potential may be derivatized with a specific feature, such as an antibody, and used as an imaging aid in a diagnostic test. When injected directly into the bloodstream it could initially show both that the molecular target was on the tumor, as well as precisely where the tumor was. This general type of approach is often used in current image-guided radiation therapies. But the power of theranostics is that, unlike with fluid contrast agents, these derivatized particles (now known to specifically target that tumor) can subsequently themselves be used as the therapeutic agent.
In theronostics these antibody-coated gold nanoparticles are injected into the bloodstream, and the particles migrate to the tumor, initially supporting in situ visualization by many means– including MRI, fluorescence, x-ray or photoacoustics. However, now the imaging particles can themselves be used to treat the tumor. In this approach, light energy, such as from a laser, can be converted into heat in the particle to kill the cancer cell. Gold nanoparticles absorb light strongly and convert photon energy into heat quickly and efficiently, thereby inhibiting or killing cells associated with it.
This makes gold particles not only a superior contrast/imaging agent, but a valuable therapeutic device as well. Because the particles that are used to identify the tumor are the same ones employed in delivering the therapy, this approach avoids most of the therapeutic target failures that can arise. Because conversion of light to heat is called plasmon resonance, this approach is known as plasmonic photo-thermal therapy (PPTT). One can imagine many different targeting molecules being employed on the particle surface, and It’s interesting that several types of gold-based nanoparticles have been employed in this, including gold nanospheres, nanoshells, nanorods and nanocages. While PPTT provides a clear example, it is only one of many very distinct ways a single technology can be used for both diagnosis and therapy (2).
Theranostics in Personalized Medicine – The future, but not so new
Such new personalized and precision forms of treatment contrast with the one-medicine-fits-all and trial-and-error medicine approaches. They better ensure that the therapy selected will be the right treatment, for the right patient, at the right time, and with the right dose. Theranostics employs molecular-based diagnostic tests and targeted therapeutics in an interdependent and collaborative manner. It provides many values, including the optimization of a therapy by producing personalized treatment through the targeting of a therapy to an individual’s specific disease subtype and genetic profile. It’s a sort of personalized-medicine / companion-diagnostic rolled into one.
Surprising to many, theranostics is over 75 years old. It began with the use of radioactive iodine (Iodine-131) for both the diagnosis and treatment of thyroid cancer. This is now a very well-established, effective and safe treatment available throughout the world. In fact, treatment centers are currently providing many different technologies with theranostic potential targeted to many different diseases (3). This combination of bioimaging and targeted drug delivery is being pursued in such indications as Cancer, Neurological Disorders and Cardiovascular Diseases.
Quite a number of cell-damaging therapeutic technologies are being considered. Beyond the PPPT approach mentioned above, duel-purpose radionuclides can provide both imaging and cell-destruction functions. In other approaches, hollow particles of many different compositions can carry potent toxins or even therapeutic medications directly to cells in the targeted tissue. In some technologies ultrasound can then be used to fuse the particle to the cell and deliver its contents.
Essentially, theranostic nanoparticles must demonstrate a targeting, visualization and therapeutic capacity. In practice, they must have a number of defined characteristics. They must be non-toxic, -immunogenic, -thrombogenic, -carcinogenic and so forth. In addition, they must also be either permanently biocompatible in all respects, or biodegradable in order to be safe for human use. They need to bind to their targets efficiently and provide such information as the biochemistry, pathology and morphology of the disease without creating collateral damage. By definition they must possess a therapeutic or toxic capacity, and finally they then must leave the body or remain within, permanently biologically inert. It’s a demanding expectation and to date no single nanoparticle has been perfect in all respects. However, the number of nanoparticles and other vehicles under consideration is quite amazing– and includes such biological nanomaterials such as proteins and DNA; many constructed organic nanomaterials such as liposomes and fullerenes; and such inorganic nanomaterials as gold, iron, silica and quantum dots.
Not only are theranostics approaches to medicine decades old, potential theragnostic nanoparticles are currently being pursued by a number of hospitals, medical center and materials providers worldwide. These include such companies as AldlabNanotech, LLC; Berkeley Advanced Biomaterials Inc; Affibody AG; Magforce Nanotechnologies AG; and NanoCarrierCo., Ltd. supporting dozens of therapies currently in clinical trial. While there are tens of nanoparticle-based agents approved for FDA clinical-trials, licensed for either imaging or therapeutic purposes, true theranostic nanoparticle applications (combining imaging and therapy capabilities) are still in their infancy.
Theranostics is actually the ultimate point-of-care medicine, where the diagnostic test closely accompanies the therapy. This is because it combines an efficient and verifiable molecular-based clinical diagnostic test with a targeted or even personalized therapeutic to provide an individualized therapy matched to a patient’s personal genetics and specific disease type, stage and response.
About the Author:
William Whitford, Strategic Solutions Leader, Bioprocess, GE Healthcare
Bill Whitford is a Strategic Solutions Leader at GE Healthcare in Logan, UT with over 20 years experience in biotechnology product and process development. He joined the company as an R&D Leader developing products supporting protein biological and vaccine production in mammalian and invertebrate cell lines. Products he has commercialized include defined hybridoma and perfusion cell culture media, fed-batch supplements and aqueous lipid dispersions. An invited lecturer at international conferences, Bill has published over 250 articles, book chapters and patents in the bioproduction arena. He now enjoys such activities as serving on the Peer Review Board for the BioProcess International.
Footnotes
This post is sponsored by Cytiva (formerly GE).