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Imagine a world where cancer is no longer seen as a death sentence, but rather as a chronic health problem that can be managed with personalised treatments. This world is closer than you might think, thanks to a revolutionary approach called radiotheranostics.
By using radiolabelled drugs targeting specific cancer cells, people with metastatic cancer can significantly improve their condition, including longer life expectancy and a better quality of life. (*Radiolabelled drugs are those which contain radioactive markers that scientists can use to follow a particular molecule.)
This approach can even lead to a long-lasting relief solution for some individuals.
But radiotheranostics is just one type of a theranostic approach that combines therapy and diagnosis to provide personalised treatments based on each patient’s tumour characteristics.
From immunotheranostics to nanotheranostics, the diversity and versatility of these treatment approaches are giving hope to cancer-affected people who previously had little chance of survival.
Boost from Imaging Technologies
Using imaging techniques such as PET scans and brachytherapy, theranostics delivers targeted therapies directly to cancer cells while sparing healthy tissue. It is akin to a precision-guided missile that homes in on the tumour and offers a highly effective and less invasive treatment option for doctors and therapy seekers.
Thanks to recent advances in imaging technology, particularly radio imaging, tumours can be precisely located in patients with aggressive cancer. Brachytherapy offers a highly precise method of delivering radiation directly to the tumour site, reducing the risk of damage to healthy tissues around it.
Recent advancements in nano(bio)technology-based imaging techniques have further expanded the diagnostic and therapeutic capabilities of theranostics. There are two possibilities in medical imaging: anatomic imaging, which provides information on the structure of organs and tissues, and molecular imaging, which provides information on cellular processes such as metabolism, protein expression, and DNA synthesis.
“These approaches enable non-invasive visualisation of the disease areas and offer valuable insights into cellular processes,” explains Dr Rajendra Prasad, assistant professor, at Interventional Theranostics and Multimode Imaging Lab, Indian Institute of Technology, Varanasi.
Dual scan PET-CT is a powerful tool in detecting even the smallest cancerous lesions and guiding personalised treatment plans based on the nature of cancer.
“Dual scans help doctors accurately stage advanced-stage cancers with multiple lesions and select the most appropriate personalised treatment,” says Dr Priyanka GB, a senior resident doctor at All India Institute of Medical Sciences, New Delhi.
These advances in imaging technology have brought us closer to the goal of providing better outcomes and a higher quality of life for cancer patients.
Nanodevices & Treatment Outcomes
Nanotechnology has the potential to revolutionise cancer diagnosis and therapy: It uses nanoparticles as specialised construction workers that can access hard-to-reach areas and carry specialised tools for diagnosing and treating cancer.
While many nanoparticle-based diagnostics and therapeutics have been tested, only a few have made it to the stage of getting the approval of the US Food and Drug Administration and reaching the market.
3 Nano types Show Promise
However, three types of nanoparticles show promise for cancer diagnosis and therapy. The first type can monitor the progress and efficacy of the treatment; the second type can be labelled with radioactive material for diagnosis and therapy; and the third type can be used for radiation therapy.
One of the most promising applications of nanodevices is in image-guided surgery. Molecularly targeted nanodevices are tiny structures designed to selectively interact with specific molecules or cells in the body, often using antibodies or other ligands (or binding molecules).
At the Imaging Physics Division at MD Anderson Cancer Center in the US Dr Ananthakrishnan Soundaram Jeevarathinam and his team are developing imaging modalities to distinguish cancer tissue from normal tissue. This is critical for guiding surgical procedures and ensuring the accuracy of tumour removal.
Precision, Low Dosage and Safety
“The same nanodevices can be utilised to deliver anticancer drugs with pinpoint accuracy, and researchers are exploring their use in modulating the immune system to enhance the body’s ability to fight cancer,” adds Ananthakrishnan
Unlike conventional chemotherapy, a nano device can precisely deliver a cancer drug to the cancer site. This means that individuals taking treatment need a much lower dose of the cancer drug than in the conventional method, and their exposure to the drug’s toxic effects is minimal, as Dr Prasad suggests. Normal tissues are also spared the toxic effects of cancer drugs.
Scientists have conducted clinical studies using special machines called PET/CT to see how well nanoparticles accumulate in tumours in breast cancer patients. They have also tested a type of nanoparticle that can be tagged with a radioactive substance to help doctors see where it goes in the body and to treat solid tumours in a small group of people.
Another type of nanoparticle has been approved in Europe for the treatment of soft-tissue sarcoma. Additionally, experiments have used nanoparticles to treat cancer using heat or light. These studies have shown promising results, and nanoparticles are being used in ongoing clinical trials.
The beauty of these nanodevices is that they can be personalised to a specific person’s biochemical signature, enabling targeted delivery of therapy.
Theranostics in Lab and Trial
Recently, the US recognised this trend and identified theranostics as a future research priority. As a result, three radiotheranostics options are available for cancer treatment especially for castration-resistant prostate cancer and for neuroendocrine tumours.
These radiotheranostics use a quantitative PET scan to determine protein expression levels, which then enables a tailored and personalised treatment approach.
“The use of radio theranostics has demonstrated significant improvements in overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer and neuroendocrine tumours, as shown in large phase 3 randomised controlled trials,” says Dr Priyanka of AIIMS.
Another radiotheranostic has been approved for the treatment of pheochromocytoma or paraganglioma in both adults and children. Other trials using theranostic radiopharmaceuticals have shown similar results in various types of cancers, including gastroenteropancreatic neuroendocrine tumours and non-Hodgkin’s lymphoma.
The development of these radiotheranostics is aligned with the growing trend towards precision medicine, which seeks to tailor both disease prevention and treatment according to the genetic, environmental, and lifestyle factors of individuals.
Shift from a Single Approach
Immunotherapy, chemotherapy, nanomedicine and radiotherapy are well-known in the field of oncology. Immunotherapy is a newer treatment modality than others, but by adding theranostic value to each approach, researchers have improved the outcomes of treatment.
Each theranostic approach provides a unique perspective and set of tools, both for diagnosing and treating cancer. Combining different approaches gives a comprehensive understanding of the tumour’s characteristics so that doctors can tailor treatments accordingly.
In cancer treatments, time is crucial as it can determine the success or failure of therapy. One of the most significant advantages of theranostics is that it reduces the time between diagnosis, treatment, and outcome monitoring.
For instance, in solid tumours, delivering drugs to the interior parts of the tumour is a challenge. Radiation therapy can be used in such cases. In some types of cancer, a specific threshold amount of drug concentration needs to be maintained at the site for an extended period. In such cases, nano theranostics allow slow and specific delivery of drugs to the tumour.
By integrating diagnosis and screening into each treatment approach, it is also possible to get insights into individual patient responses to specific theranostic approaches and adjust them accordingly. “This approach is a move away from the traditional one-size-fits-all approach towards a tailored approach guided by scientific evidence,” adds Ananthakrishnan
Cost and Access to Theranostics
The cost of cancer treatment can be a major burden for families in countries like India. New treatments that are emerging often come at a very high cost. While there have been some successes in cancer theranostics with a couple of therapies approved for the clinical trial, the reality is that their access is limited.
For instance, a new drug developed for HER2-positive breast cancer has shown promising results, but its high cost raises concerns about its accessibility and affordability. People can access cancer theranostics only in advanced institutes that provide this treatment after giving their voluntary approval.
It is crucial to prioritise developing theranostics for cancer, particularly in countries like India. However, safety should always be the top concern, which may lead to developmental delays.
AI, ML and Regulatory Cycles
Regulatory bodies worldwide mostly follow the US FDA for cancer treatment approvals. The FDA for its part has been cautious about approving theranostics for cancer treatment, putting safety first
For instance, Novartis’s radiotheranostic drug was approved for the treatment of prostate cancer in March 2022. However, the drug’s development started in 2012, and its preclinical development was first reported in 2005.
It is only heartening that regulatory bodies critically view every stage of a drug’s development, and not just its ability to mitigate or kill cancer cells – but therein lie the delays. However, with the arrival of artificial intelligence and machine learning, the time taken in drug development is expected to reduce significantly soon.
This, combined with the establishment of clear regulatory and safety guidelines, can help expedite the commercialisation of nanoparticle-based imaging and therapeutics, paving the way for far more effective cancer treatments than at present.
Challenges and Opportunities
The development of targeted anticancer nanomedicine, or theranostics, faces several challenges. While there have been modest improvements in patient outcomes, there is still a lack of substantial success with these solutions.
“One of the main issues is the low percentage of imaging and therapeutic encapsulated platforms [ITEP] that reach tumour sites,” adds Dr Prasad.
Nanoparticles can aggregate or be eliminated by immune cells and cleansing organs, and current theranostic particles have not been successful in solving this problem in pre-clinical and clinical models.
Experts advise that to improve these solutions, it is crucial to determine the factors that contribute to their enhanced performance in specific tumour areas. This understanding may be linked to the molecular-level manufacturing of nanoparticles.
Furthermore, medical practitioners should be provided with guidelines for the selection, handling, and utilization of nanomedicines. Additionally, existing guidelines should be expanded to encompass the use of nanomedicines.
In India, they are accessible in central government-run institutes, but peripheral healthcare institutes lack the necessary resources to provide this precision-guided approach, notes Dr Priyanka. In the private sector, the cost of a theranostics treatment is often prohibitive and puts it out of the bounds of many people who need it most.
In India, agencies such as Atomic Energy Regulatory Board (AERB) in India have guidelines for running a theranostics facility, but bureaucratic delays can slow down the implementation.
Finally, a collaboration between industry and academia is essential for identifying and testing new agents to support the widespread use of tracers and other theranostics technologies.
