The term “theranostics” is a combination of “therapy” and “diagnostics“; it is an emerging field that combines into a single platform both diagnostic and therapeutic capabilities. In particular, it involves using one radioactive drug to identify and diagnose tumors and another to deliver therapy.
It aims to provide personalized and precise patient treatment strategies by tailoring therapies based on individual characteristics and disease profiles. This way, the probability of a favorable outcome is improved, and the likelihood of an adverse event is reduced. This integration of diagnostics and therapeutics holds great promise for the future of precision medicine. Here’s how theranostics is shaping the landscape of personalized healthcare:
The Diagnostic Phase
To diagnose the presence of a tumor, we need to identify diagnostic drugs that target tumor cells. Often, membrane proteins such as the somatostatin receptor (SSTR2) that are present on the tumor cell surface can provide an optimal target for diagnostic molecules. Indeed, it is possible to design radioactive drugs that target SSTR2. Usually, the drug is injected into a patient’s vein and travels through the bloodstream to all body tissues. If the patient has a tumor, the ligand can recognize and bind to the membrane protein, highlighting its presence on a PET scan.
I would specify here that these “cancer drugs” you are talking about in this section are for diagnostic purposes, since it sounds as if they are meant to kill the tumor.
The Therapeutic Phase
Once the tumor has been diagnosed using the radioligand, it is possible to design a therapeutical molecule to target and kill the tumor cells that express the target protein on their membranes. The radioligands designed for therapy differ from the ones used for diagnostics because they release radiation in distinct ways. While diagnostic radionuclides emit electromagnetic radiation (gamma rays), which Indeed, the therapeutic radioligands emit high-energy radiation able to break the DNA bonds of the cancer cells, thus killing them. One benefit will be that healthy cells surrounding the tumor would not be affected by the killing abilities of the drug.
PSMA: a Potential Theranostics Drug
A notable example of integration among diagnostic imaging and radio-ligand therapy is 68-Ga-PSMA. 68-Ga-PSMA is a radioligand currently used to diagnose prostate cancer. PSMA is a prostate-specific membrane antigen highly present on the surface of prostate cancer cells and the ideal marker to identify the tumor through PET. A small ligand for this antigen is marked with Gallium-68 so that the tumour and metastatic areas are visible once injected into the patient.
The same molecule could be marked with an appropriate radionuclide (177Lu, for example) so it could be used for therapeutic purposes: the drug is injected into the patient, and it will localize within the tumor, exerting its activity in a very precise and localized way.
Future Perspectives
Theranostics has already been used for neuroendocrine and thyroid tumors, and just recently, FDA has approved 177Lu-PSMA-617 (commercial name PLUVICTO) for the treatment of prostate cancer.
The applications of this approach are endless, and the advantages are numerous. One of the key benefits of theranostics is its ability to improve the accuracy of disease diagnosis. Traditional diagnostic methods, such as ultrasounds, CT scans and blood tests, can provide limited information about a patient’s condition. In contrast, theranostics can identify specific biomarkers associated with a particular disease, allowing clinicians to make more precise diagnoses. For example, theranostics imaging can detect tumors early and determine whether they are malignant or benign.
In addition to improving diagnosis, theranostics can also enhance the effectiveness of treatment. By identifying the molecular profile of a patient’s tumor, clinicians can select the most appropriate therapy for that individual. For example, HER2-positive breast cancers can be treated with drugs targeting the HER2 protein, improving survival rates.
Theranostics can also help to reduce the likelihood of adverse events associated with the treatment. Traditional radiation therapies and chemotherapies are associated with significant side effects, such as nausea, fatigue, and hair loss. Clinicians can minimize the risk of these side effects by selecting the most appropriate therapy for a particular patient. In addition, theranostics can help identify patients at risk of developing adverse events, allowing for early intervention and prevention.
Even if theranostics seems to be an ideal tool to improve cancer treatment—personalized and tailored for each patient—some challenges are still to be overcome. First, physical side effects, including appetite loss, fatigue, and nausea, are still present. Theranostics allow precise radiation delivery to abnormal tissues, reducing the risk of radiotherapy-related complications. However, radiation exposure has been linked to other types of cancer. In addition, identifying new biomarkers that can be used to target cancer cells is still difficult, and the validation and protocol standardization processes follow a long and complex path.
In conclusion, theranostics represents a transformative medical shift where diagnostic and therapeutic strategies converge to provide personalized, effective, and precise healthcare solutions. As research and technology progress, theranostics is likely to revolutionize the field of precision medicine and significantly impact patient care and outcomes.
References:
[1] Nuclear Medicine in the Treatment of Cancer – Kvalito
[2] 5 Things to Know about PSMA-PE, (2020) Prostate Cancer Foundation 5 Things to Know about PSMA-PET | Prostate Cancer Foundation (pcf.org)
[4] Prostate-specific membrane antigen (PSMA)–ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer (2020), Prostate-specific membrane antigen (PSMA)–ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer – PMC (nih.gov)
[5] [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study, (2018) The Lancet Oncology [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study – The Lancet Oncology
[6] What is theranostics? | University of Iowa Hospitals & Clinics (uihc.org)
[7] Theranostics – UChicago Medicine
[8] Prostate Cancer Theranostics: PSMA Targeted Therapy, (2021) PET clinics Prostate Cancer Theranostics: PSMA Targeted Therapy – PubMed (nih.gov)
[9] What is Theranostics?, (2023) Journal of Nuclear Medicine What Is Theranostics? | Journal of Nuclear Medicine (snmjournals.org)
[10] PET con PSMA per il tumore alla prostata: in Humanitas l’innovazione della Teranostica – Humanitas
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