Targeted Radionuclide Therapies (Theranostics)

In nuclear medicine, stable and unstable isotopes, which do not undergo radioactive decay over time, are used for therapeutic purposes. In pharmacokinetic research, stable isotopes are mostly utilized as tracers to examine human metabolic processes. Since the tailored synthesis of novel carbon-13, nitrogen-15, and oxygen-18 radiolabeled compounds as well as noble gas isotopes is actively expanding, stable isotopes currently play a significant role in current medical research and have considerable potential for future research applications. Unstable isotopes are characterized by an overabundance of neutrons that interact with the protons in their nucleus, explaining both their ability to release ionizing radiation and their decay, as indicated by their half-life. A and/or an electron or positron emission, along with energy emission manifested as gamma rays (electromagnetic radiation), are generally used to stabilize radioisotope nuclei.

The current study examines radionuclide therapy in oncology and identifies emerging trends. A nuclear reactor's neutron activation process can create 3,800 radiation-emitting isotopes, as can other nuclear reactions in a cyclotron or linear accelerator. Less than 50 radioisotopes are routinely utilized in clinical settings, and about 200 have been studied for possible medical uses. Over 10,000 hospitals worldwide regularly employ radioisotopes for diagnostic purposes, with a prevalence of about 90%. More specifically, diagnostic nuclear medicine procedures are employed with a frequency of 2% per year in 26% of the world's population, or the approximate population of developed countries, with radioisotope therapy accounting for roughly one-tenth of these procedures. In the US, more than 20 million nuclear medicine procedures are conducted annually on 311 million people, compared to around 10 million procedures on 500 million individuals in Europe.

 

Theranostics

A new term called theranostics was coined to describe medications and devices used for simultaneous diagnosis and treatment, or, to put it another way, diagnosis plus therapy. In the 1940s, the idea for the first theranostics-based therapeutic application was developed for patients with metastatic thyroid cancer using radioactive iodine therapy. Following this, various radioligand-based treatments have gained popularity in early-phase clinical trials, particularly for PSMA-expressed prostate cancer. These treatments include radio-attached monoclonal antibodies, small-molecule inhibitors of prostate-specific membrane antigen (PSMA), and emitting radioisotopes. With approximately 10 million new cases each year, cancer is one of the top five primary diseases that killed millions of people in the 20th century and is still difficult to treat. It also causes severe morbidity and/or mortality. Traditional radiotherapy and chemotherapy have been the mainstays of cancer treatment for many years, but these treatments have several downsides and side effects, including a major negative impact on non-cancerous cells. Many treatment strategies are still said to be inefficient at avoiding recurrences, despite recent medical improvements in the form of targeted therapies, early identification, and behavioral modifications that have improved cancer prognoses. Furthermore, these treatment methods' invasiveness, medication resistance, and systemic toxicity side effects are heavily debated. Theranostics is a cutting-edge medical concept that replaces the traditional one-size-fits-all medical method with a more holistic, individualized approach. With the proper dose and a more focused and effective pharmacological profile, this therapy aims to provide the right care for the right patient at the right time. It is crucial to concentrate on factors such as adequate blood plasma circulation time, targeted delivery to cancerous tissues only while successfully avoiding accumulations in normal tissues and organs, lack of an immune response, concurrent treatment, and non-invasive monitoring for effective drug delivery when creating these theranostic-based technologies for clinical translation. Additionally, it would be ideal if the distribution method was non-invasive, non-toxic, and biodegradable.

 

Theranostics and Nanomedicine

Nanomedicine, the term for the use of nanotechnology in medicine, is made possible by a wide variety of scientific and medical approaches. Theranostics using nanoparticles is one such method. Theranostics and nanomedicine are being combined with the ultimate goal of dramatically improving illness and patient-specific results.

Nanoparticles have substantial advantages and are ideally suited for use in theranostic medicine because of their great potential to target specific organs or tissues and their ability to be modified with multi-functionality.

According to the preceding sentence, nanoparticles can target sick areas of the body without harming healthy parts. The extent of the disease and, if relevant, the disease's response to treatment may be shown by nanoparticles after the area of interest has been identified. Nanoparticles can then carry out the therapeutic delivery as necessary after collecting this information.

These nanoparticles can provide precise therapeutic drug concentrations based on responses to internal or external stimuli. They may also contribute further to the monitoring of drug delivery, release, and efficacy.

Unlike many conventional pharmacological therapies, nanoparticles can avoid being prematurely destroyed or degraded by physiological processes. Additionally, nanoparticles' high surface-to-volume ratios make it possible for them to transport a wider variety of compounds while using less unnecessary material. Nanoparticles can be very useful in the detection and treatment of cancer.

They are perfect in this regard since they can quickly and intentionally aggregate at cancer-specific areas, emit signals based on their specific biomarkers once there, and then administer the required medication with the information they collected.

 

The Application of Theranostics in Cancer

Cancer is a complex concept because it encompasses a variety of disorders that are all defined by uncontrolled and fast cell proliferation. Typically, affected patients' genetic and/or epigenetic abnormalities are to blame for this. Chemotherapy, radiotherapy, immunotherapy, and surgery are currently used as cancer treatments.

Due to the low concentration of medication molecules that reach the tumors they are meant to cure; chemotherapy is particularly ineffective. The emergence of treatment resistance throughout therapy and, of course, the numerous side effects related to the medications used are additional disadvantages of chemotherapy.

Here, the use of nanoparticles in nanomedicine demonstrates significant promise for overcoming the drawbacks of conventional therapy. These particles enable molecular targeting, ensuring increased medication molecule concentrations at the tumor site. In recent years, in-depth research on drug delivery methods utilizing nanotechnology has focused on this. This research looks into the active or passive usage of nanomedicines to trigger drug release at specific sites. Preventing the drug from reaching off-target tissues, raises the therapeutic index.

Polymeric micelles, polymer-drug conjugates, and liposomes are a few examples of nanomedicines that have substantial clinical value. Nanomedicines have longer half-lives than conventional small-molecule medications, which are quickly removed from the bloodstream.

They also have enhanced tumor delivery and higher absorption. Additionally, the potential incorporation of imaging into nanomedicine will help with theranostics' diagnostic component. Researchers could advance the use of theranostics in the treatment of oncogenic diseases by using this approach, which has several benefits.

 

Examples of Theranostics

• Radioactive iodine therapy. In differentiated thyroid carcinoma (follicular and papillary), the therapeutic use of iodine-131 (I-131) is a well-established method that complements surgery.
• Peptide receptor radionuclide therapy. Adult patients with neuroendocrine tumors who are inoperable, who still have the disease after resection or other ablative therapy, or who have metastases, should get peptide receptor radionuclide therapy (PRRNT).
• Selective internal radiation therapy. Patients with primary and secondary liver cancers that cannot be surgically removed may benefit from selective internal radiation therapy (SIRT) or trans-arterial radio-embolization utilizing Y-90-labelled microspheres.
• Radio-immunotherapy. In first-line or successive lines of therapy, follicular B-cell lymphomas expressing the CD20 epitope can be effectively treated with radioimmunotherapy (RIT).

 

Theranostics Benefits

Although theranostic therapies generally do not treat cancer, they do improve patients' quality of life and length of life for those who may require additional therapies. The concerns of side effects to patients from theranostic treatments are generally surpassed by the benefits, which include a decrease in cancer-related symptoms.

 

Theranostics Candidates

For a metastatic disease that does not respond well to recognized systemic therapies like traditional chemotherapy, there is currently a treatment alternative called theranostics. You may be fit for theranostics if those stop working. To determine whether your tumor can be targeted by the tracers, doctors first perform a PET scan; if the result is positive and the tumor is broad, you are a candidate. Selective therapies like surgery, external beam radiation, or embolization, in which the tumor's blood supply is cut off by an interventional radiologist, might be more successful if your tumor isn't widespread.

 

Cancer Treated with Theranostics

A pair of radioactive iodine tracers for thyroid cancer is among the earliest, most reliable theranostics that are still widely used today. This technique has been carried out effectively for many years, and it continues to be a valuable tool in the inventory for the treatment of thyroid cancer. This theranostic procedure is taken orally, as opposed to other theranostic procedures that are supplied intravenously. Advanced biochemistry is used in contemporary theranostic medicine to cure tumors like:

• Neuroendocrine cancer. The use of Lu 177 dotatate (Lutathera), in particular, has transformed how physicians treat neuroendocrine tumors, particularly carcinoids. The somatostatin receptors on the tumor cells are the target of the dotatate.
• Prostate cancer. Patients with castration-resistant prostate cancer who have previously received androgen receptor pathway inhibition and taxane-based chemotherapy are treated with Lu 177 vipivotide tetraxetan PSMA (Pluvicto). Every six weeks, patients receive an infusion, for a total of six sessions. Many hospitals in the world participated in the Lu 177 PSMA managed access program before the FDA approved it.
• Neuroblastoma, paraganglioma, and pheochromocytomas. I131-iobenguane/MIBG (Azedra) is used to treat neuroblastoma in children and pheochromocytoma and paraganglioma in adults.

 

How Do Theranostics Work

A radiotracer is made up of two parts: the biological side goes through the blood to bind to a specific, predetermined target, in this example, a particular kind of cancer cell. The radioactive part is the other half. This radioactive component produces a small amount of radiation during the diagnostic scan that enables doctors to image the cancer cells that the radiotracer has attached itself to. The biological aspect of the treatment is essentially the same, but the radioactive component uses a different, more potent radiation that kills cancer.

The biological side must bind to that particular target on the tumor cells during both the diagnostic and therapeutic procedures. The radiotracers do not attach to healthy cells since the majority of other healthy cells lack that target.

 

What Happens During Theranostic Procedure

The radiotracer is first administered intravenously to patients in either their hand or arm. At the PET Center, this chemical liquid is delivered. You will lie on the PET table as the scanner examines your body for cancer cells after around an hour has passed while the radiotracer absorbs and binds to cancer cells.

The scan results will demonstrate the presence of cancer and its location throughout the body. Your cancer doctor will receive a report from the nuclear medicine specialist who analyzed these images and use it to determine whether to proceed with the follow-up treatment radiotracer that specifically targets and eradicates the cancer cells identified on the PET scan. Typically, this infusion only takes a few minutes, followed by a period of observation. It is performed in the infusion therapy suite, which has unique treatment rooms created specifically for theranostics treatments. Then you can return home. The radiation is eventually excreted through human fluids after a few days.

 

Theranostics Risks

Even though the radiation is carefully targeted, the fact that your body is exposed to it can marginally raise your risk of getting another cancer. Because the medication can stun your bone marrow, where blood cells are created, one frequent adverse effect is that levels of specific blood cells may somewhat fall. Usually, this is just temporary. Some individuals report feeling worn out and having gastrointestinal issues, including nausea and appetite loss.

Other adverse reactions are more treatment-specific. For instance, because their salivary glands receive some radiation during PSMA prostate cancer therapy, patients may develop dry mouth. All of these potential negative effects are monitored by your doctor. After each infusion, doctors check your blood counts to make sure your blood cells are handling the medication well.

 

Conclusion

In conclusion, 131I is no longer the only effective radionuclide therapy for cancer, and a new, hopeful era of novel radiopharmaceuticals targeted specifically against malignancies is actively emerging, with the promise to improve patient care and results. The development of highly specialized and complex techniques like radioimmunotherapy expands the treatment options and opens the path for individualized medicine. But this field's full potential is still far from being realized. To clarify the possible contribution of radionuclide therapy to therapeutic efficacy in comparison to traditional therapeutic plans, randomized double-blinded multicenter prospective studies are required.