What is theranostics in nuclear medicine? Theranostics is a new term in the field of medicine, but gaining considerable traction.

The concept of theranostics refers to the integration of therapeutics and diagnostics in one package. For example, with imaging and therapy merged, follow-up treatment and therapy can happen simultaneously.

Importantly, theranostics promotes patient-centered care and more personalized treatment. Where therapeutic intervention can be personalized, it can help to avoid unnecessary therapies being given to a patient for whom they are not suitable and ensure that the targeted therapy area is will be impacted by the planned therapy.

Characteristics of theranostics

Theranostics includes a few different modes that have two main components – the diagnostic and the therapeutic. Let’s take a closer look:

Diagnostic component

“The diagnostic component may be a radiotracer, a contrast agent molecule, a particulate system with an inherent physical property (e.g., optical, magnetic) or an acquired physical property (e.g., contrast-enhanced ultrasound property), or combinations thereof (allowing for dual or multimodal imaging).” (source)

Here are some examples:

• Radio tracers – gallium-68 and scandium-44 used in PET/CT
• Contrast agents – gadolinium (III) used in MRI
• Particulates – gold nano-particles, gold nano-rods, quantum-dot nanochrystals, iron oxide core-shell nanoclusters
• Combination – surface-bound gadolinium(III) compounds (for dual ultrasound and MRI) and magnetic nanoparticles containing fluorescent probes (MRI and optical imaging).

Therapeutic component

The therapeutic component generally involves a drug molecule that is either directly linked to the diagnostic component or is associated with a carrier system. For the majority of the theranostics being developed in nuclear medicine, the chemical composition of the radiopharmaceuticals being used for diagnostic imaging and therapy are the exact same, with the exception of the isotope being swapped out. This ensures that the biodistribution remains the exact same throughout the imaging and therapy portions while delivering a, typically, higher dose of radiation to the targeted treatment area.

Some linked examples include:

• Peptide-based molecules (e.g., Y-90 or Lu-177-labeled somatostatin analogs for somatostatin receptor targeting in neuroendocrine tumors, gallium-68-labeled affibody)
• Nanobody molecules targeting human epidermal growth factor receptor and drug molecules covalently coupled to iron oxide or gold nanoparticles with appropriate coatings.

Some carrier examples include:

• Polymer construct, a plasma protein such as albumin, or an antibody or a supramolecular assembly (e.g., a dendrimer) that also carry covalently attached diagnostic components.
• Drug molecules that are co-encapsulated with diagnostic components, for example, chelated radiotracers and gadolinium(III), quantum dots, gold nanoparticles.

Implications for patient care

One of the big implications for patient care is that theranostics represents a transition from conventional medicine to personalized medicine. Custom-made treatment plans can be devised that are as unique as the individual, meaning the right drug is administered to the right patient at the right time.

On the flipside, new diagnostics can be used to identify patients for whom a drug is unlikely to work as well. For example, some drugs show efficacy, but not for all patients with the same condition. Theranostics can help to determine which patients may benefit from a particular treatment, speeding the time taken to find an effective treatment and saving them the costs of those that are likely to be ineffective.

Genetics play a big role in theranostics, emphasizing how genetic variations can indicate risk for specific diseases and the likelihood of successful treatment. This has given rise to the following areas of study for theranostics:

• Pharmacogenetics – This studies the individual variations in DNA sequences and responses to treatment interventions by biomarker. This helps to tailor drug therapy.
• Proteomics – Comprehensive analysis and characterization of all of the proteins and protein isoforms encoded by the human genome. This plays a vital role in tailoring therapies for the physiological aspects of the cells.
• Biomarker profiling – This helps to optimize treatments for each individual patient. Patients may experience reduced side-effects and improved response to treatment. As one study puts it, “today’s biomarker is tomorrow’s theranostics.”

Theranostics can take diagnosis from the lab to the patient point-of-care. This can allow for faster diagnosis, avoiding situations such as lab back-ups. Patients can benefit from receiving more expedient care.

As a related benefit in medical imaging, use of theranostics can reduce or eliminate the need for patient preparation, such as fasting or reclining during uptake. An example of an radiopharmaceutical that is being developed is FAPI-PET/CT, which can outperform a FDG-PET/CT in this way, with a short patient uptake time. From the patient perspective, this can improve comfort, while for the physician it can accelerate workflow.

The concept of “patient-centered care” has been a predominant practice over the last few years. Clinics frequently have goals and requirements around patient-centered care and its flow-on impacts for key metrics such as readmissions, patient satisfaction and average length of stay. Theranostics promises to be a helpful tool in the provision of patient-centered care, with the potential to improve many key hospital metrics.

Theranostics in action

Here are some current examples of how theranostics are used in practice:

Oncology is one of the major areas for theranostics. For example, a specific diagnostic test shows a particular molecular target on a tumor, allowing a therapy agent to specifically target that receptor on the tumor, rather than more broadly the disease and location in which it presents.

In medical imaging, theranostics are on the rise with the use of various radiotracers. For example, the recent SNMMI “image of the year” winner showcased the efficacy of the FAPI radiotracer in over 30 epidemiological tumor entities. Here is an extract from their report:

“In addition to identifying tumors, the research is also important for the development of cancer treatments in the future. “Immunotherapies can be highly effective in some patients and without any anti-tumor activity in other patients,” noted author Uwe Haberkorn, MD, professor and chair of nuclear medicine at the University Hospital of Heidelberg and the German Cancer Research Center in Heidelberg, Germany. “Currently, predictive biomarkers for appropriate patient selection are limited. Due to its biological role, FAP-targeted diagnostics has the potential to be a predictive biomarker.”

Prof. Haberkorn continued by noting that “The used FAP-ligands contain the DOTA-chelator, which enables labeling with therapeutic radionuclides. The observation that the ligand accumulates in several important tumor-entities potentially indicates a huge field of therapeutic application to be evaluated in the future.”

• Defining and selecting combination drug therapy protocols.
• Stimuli-responsive theranostics can facilitate drug release at the right time in patients.
• Drug responses and adverse effects are predicted, particularly in oncology. “Opening new vistas in cancer management in three dimensions – diagnosis treatment and monitoring the response is the application of theranostics, especially with the support of nanotechnology.” (source)
• Monitoring local drug-release processes.
• Non-invasive determination of biodistribution and evaluation of dynamics processes at target-site accumulation.

What is Next for Theranositcs

Technically-speaking, theranostics has been around for decades, since the use of radioactive iodine (I-131) or Iodine-131 Therapy for the diagnosis and treatment of thyroid cancer. The term “theranostics” is more recently credited to John Funkhouser and has been undergoing many advances through technological discoveries.

Theranostics represents huge leaps in patient care and the possibilities for more personalized therapies. Some known benefits include a shift away from “one medicine fits all” for a disease diagnosis and toward medicines tailored for the make-up of the individual. This can mean more effective therapies, more cost-effective treatments and overall improved outcomes.

Theranostics can be described as “P4 medicine,” meaning that it is predictive, preventive, personalized, and participatory. It all adds up to better clinical care, with the promise of further developments to come.