Theranostics for cancer

 Theranostics is a portmanteau – a mashup of therapy and diagnostics. It’s a hot area of research now, but has yet to yield significant results in the clinic. Promoters claim it will eliminate steps in the cancer management process and bring quicker treatment to patients.

The idea is a technology that could do all or part of a diagnosis – identifying a disease or finding malignant cells – along with all or part of a treatment to attack the disease. For instance, scientists imagine tiny particles that can both diagnose disease and deliver treatment – perhaps to deliver treatment only to malignant cells.

iv administationFor instance, imaging technology could be combined with delivery of chemotherapy agent or nucleic acids (gene therapy), or radioactive particles. Proposed systems use “nanoplatforms” that can travel through the bloodstream.  Chemotheranostics is another word some are using to refer to theranostics employing a chemotherapy agent. Proposed diagnostic techniques include fluorescence imaging (using aggregation-induced emission fluorogens, or AIEgens)  and optoacoustic imaging to guide the chemotherapy agent.  Other scientists are investigating the use of free radicals for both diagnosis and treatment.

So far few theranostics have found their way into medical practice. Research is focused on platforms. Scientific papers are published about work on nanoshells, plasmonic nanobubbles, and other innovative devices.

Magnetic nanoparticles (MNPs) have been used to enhance the contrast in magnetic resonance imaging.   Scientists are looking at ways of converting them to therapeutics, too.  Chinese scientists have created magnetic liquid metal nanoparticles that facilitate CT/MR imaging and can be loaded with a drug; these may someday be used in transcatheter arterial chemoembolization in treatment of liver cancer.  Other scientists have looked into carbon nanotubes as well as gold. silica, and black phosphorus nanoparticles. Theranostics are an exciting tool especially in drug development where they allow researchers to look into the kinetics of drug movement and the efficiency of the therapy. Researchers load imaging agents used in other diagnostic systems (fluorescent materials, MRI, PET/SPECT) onto nanoplatforms to figure out what happens at a cellular level.  So-called “smart nanoparticles” morph size and shape in response to their environment, and these may be amenable to reacting to physiological microenvironments around tumors, making them good theranostics.

Iodine-131 and Iodine-132 combined with the ligand octreotide are approved and in use.

Lutetium-177 docecate was approved by the FDA in 2018 and is considered a theranostic technology.  Lutetium-177 has a half-life of 6.6 days and emits Beta radiation.  The conjugate Ga-68 DOTATOC is similar and used in positron emission tomography imaging of neuroendrocrine tumors, but Ga-68 DOTATOC is not considered a theranostic.  Replacing the Gallium atom with a Lutetium atom makes a theranostic that has the potential to kill malignant cells.  DOTA is dodecane tetraacetic acid. DOTATOC is DOTA octreotide.

Combinations of Fluorine-14 and of Iodine-123 with PARP inhibitors are in clinical trials.  Combinations of Actinium-225 and Indium-111 with monoclonal antibodies are also in trials.

Many theranostic technologies employ a radioactive material and hence bring a risk of leukemia and myelodysplastic syndrome.  Even when no secondary cancers form, precaution limits the number of lifetime doses that a patient can receive.

There has been criticism that the term theranostics should not be used as it papers over the division between diagnosis and therapy.  The concept of linking diagnosis and therapy is not new; the nano scale at which these new technologies do so is the innovation.  And arguably theranostic technologies are a form of targeted therapy – a very precise targeted therapy but still another targeted therapy.