The integration of theranostic agents marks a significant milestone in cancer therapy, embodying the principles of precision medicine and molecular targeting. These compounds, with dual diagnostic and therapeutic capabilities, represent a paradigm shift in cancer treatment strategies. Theranostic drugs consist of a biologic component that binds to a specific molecular target in a patient’s tumour, making them ideal for the current focus on precision medicine. The biologic component of a theranostic drug can be labelled with positron emitters for PET imaging or beta and alpha emitters for radionuclide therapy.
In clinical practice, theranostic drugs have shown significant applicability in prostate cancer and neuroendocrine tumour therapy, with continuing research into their efficacy across diverse cancer types. In 2018, FDA approved 177-Lu DOTATATE for the treatment of metastatic neuroendocrine tumours of the pancreas and midgut. 177-Lu DOTATATE, an agent in which a lutetium radioisotope is coupled to a biological protein that particularly targets peptide receptors, such as somatostatin, which are overexpressed in neuroendocrine tumours. Four years later, FDA approved 177-Lu-PSMA-617, an agent that targets the prostate-specific membrane antigen (PSMA), to treat metastatic castrate-resistant prostate cancer.
Theranostic drugs offer an additional systemic therapeutic option for cancer patients who have already undergone chemotherapy and/or immunotherapy. Recent research indicates that they may be more beneficial when administered before chemotherapy for prostate cancer patients.
Theranostic agents, unlike EBRT, offer systemic treatment targeting tumors expressing specific markers, potentially reducing damage to surrounding healthy tissue, but may cause systemic side effects like bone marrow toxicity. When compared to EBRT, theranostics offer a lower radiation dose over a longer period of time. This enables tissue and DNA repair, thus normal organs can withstand more doses than they would with EBRT. While dosimetry is commonly used in the planning of EBRT and brachytherapy, it is more complicated for radionuclide therapies due to patient-specific variation in tumour distribution, variable biodistribution and kinetics of the radiopharmaceutical, and difficulties in accurately quantifying radiation from SPECT systems.
In comparison to Chemotherapy, Radionuclide therapy is a more targeted and personalised method that is typically more bearable and has fewer adverse effects. For example, Lu-177-PSMA-617 for prostate cancer has been demonstrated to have less side effects than standard-of-care chemotherapy.
Improvements in dosimetry and the use of new radiopharmaceuticals are set to improve theranostic treatments. Targeted alpha-particle therapies show potential by targeting tumours while protecting nearby healthy tissues. Combining theranostics with chemotherapy and immunotherapy opens new treatment avenues. Though limitations exist, these advancements offer hope for better cancer treatment in the future.
