Tin-117m DOTA-Annexin V: A Theranostic Agent for Vulnerable Plaques, Cancer, Rheumatoid Arthritis, and Alzheimer’s Disease

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Summary: Tin-117m DOTA-Annexin V represents a remarkable fusion of molecular biology, radiochemistry, and therapeutic potential. Labelled with the radioisotope Tin-117m, this agent marries the targeting specificity of Annexin V with the unique properties of conversion electron emissions. It has demonstrated promise not only in imaging vulnerable plaques in atherosclerotic disease but also in offering a targeted therapeutic approach to conditions ranging from certain cancers to rheumatoid arthritis. Ongoing clinical studies have already confirmed its ability to image and identify high-risk atherosclerotic plaques in human vessels, and future directions include potential therapy for Alzheimer’s disease through targeted microglial destruction. In this article, we explore the key principles behind Tin-117m DOTA-Annexin V, its mechanism of action, clinical progress, and anticipated clinical relevance.

Keywords: 117mSn-DOTA-Annexin V: Theranostic: Vulnerable Plaque; Conversion Electron; Annexin V; Alzheimer’s Therapy.

Introduction to Cardiovascular Diseases

Cardiovascular diseases, particularly atherosclerosis, remain a leading cause of morbidity and mortality worldwide. Atherosclerosis entails the build-up of plaques within the arterial walls, which can become inflamed, weaken, and eventually rupture. Plaque rupture is a major culprit behind heart attacks and strokes, often occurring without warning. Presently, standard diagnostic tools such as CT scans, MRI, and ultrasound are limited in their ability to detect which plaques are most likely to rupture. The urgent need for precision diagnostic and targeted therapy has fuelled the rise of theranostic agents—substances that can be used both to image diseased tissues and deliver targeted therapy.

One such revolutionary agent is Tin-117m DOTA-Annexin V, which combines the capabilities of Annexin V, a naturally occurring protein, with the radioisotope Tin-117m (117mSn). This agent has demonstrated its capacity to bind to certain cells and tissues that are typically hallmark features of cardiovascular disease, cancer, rheumatoid arthritis, and neuroinflammation.

The synergy between the specificity of Annexin V and the radiological profile of Tin-117m offers clinicians and researchers a new approach in diagnosing and treating life-threatening conditions.

In this article, we will explore the science behind Tin-117m DOTA-Annexin V, the biology of annexin binding, the role of conversion electron emissions, ongoing clinical studies, and the future landscape of this exciting technology, including its implications in Alzheimer’s disease.

Tin-117m DOTA-Annexin V: Composition, Labelling, and Mechanism of Action

Theranostic agents require a targeting molecule and a radioactive label capable of diagnostics and therapeutic impact. In the case of Tin-117m DOTA-Annexin V, Annexin V serves as the biological carrier/ligand, while the 117mSn radioisotope delivers both imaging clarity and therapeutic action.

Composition and Labelling

  • Annexin V: A member of the annexin family, Annexin V is known for its high affinity for phosphatidylserine (PS), a lipid typically located on the inner leaflet of the cell membrane. When cells undergo apoptosis or become inflamed, PS is exposed on the outer membrane surface, attracting Annexin V.
  • DOTA Chelator: The diethylenetriaminepentaacetic acid (DOTA) analogue acts as a robust chelator. It securely holds the metal radioisotope, preventing it from freely circulating and causing non-specific radiation damage.
  • Tin-117m: The 117mSn radioisotope is unique for its conversion electron (C.E.) emissions. Conversion electrons possess shorter tissue penetration depth compared to gamma rays, allowing for targeted energy deposition and minimal collateral damage.

Process of Labelling:

  • The DOTA chelator is conjugated to Annexin V.
  • Tin-117m is then introduced to the DOTA-Annexin V complex, forming a stable bond that retains its targeting function without altering the molecular properties of  Annexin V.

Mechanism of Action

Annexin V Binding: Annexin V identifies cells in pathological states—such as apoptotic cells, activated endothelium, or inflamed macrophages—by binding to externalised phosphatidylserine. In conditions such as atherosclerosis, large quantities of macrophages accumulate in plaques, many of which present phosphatidylserine as they become dysfunctional or die. This acts as the main anchor point for Annexin V.

117mSn Radiation: The key to theranostic capability of 117mSn lies in its conversion electron (C.E.) emissions. These electrons travel only a short distance within the tissue, leading to localised radiation damage to the targeted cells. This can ultimately shrink or “dissolve” pathological plaques, kill cancer cells, or modulate the immune response in autoimmune diseases like rheumatoid arthritis. When combined with imaging techniques such as Single Photon Emission Computed Tomography (SPECT), clinicians can simultaneously visualise and treat diseased tissue.

Imaging Vulnerable Plaques

Heart attacks and strokes can occur abruptly, triggered by the rupture of an atherosclerotic plaque. Traditional imaging modalities (such as angiography, ultrasound, CT, or MRI) can provide structural details but often cannot distinguish truly “vulnerable” plaques from more stable ones. Identifying the specific region of greatest risk is a challenge that has, until now, gone largely unmet.

Advantages of 117mSn-DOTA-Annexin V in Plaque Imaging

Targeting Inflammatory and Apoptotic Cells: The pathological processes driving plaque vulnerability are intimately tied to inflammation and cellular apoptosis. By binding to phosphatidylserine exposed on the surface of such cells, 117mSn-DOTA-Annexin V effectively illuminates the plaques that pose the greatest danger of rupture.

Enhanced Sensitivity and Specificity: Because Annexin V only binds to sites of damage or inflammation, the resulting signal is more specific than traditional radiological contrast agents. Furthermore, the short-range emission of conversion electrons minimises off-target radiation, which could otherwise degrade diagnostic clarity.

Clinical Evidence

A Phase II clinical trial has been underway to evaluate the safety and imaging capability of 117mSn-DOTA-Annexin V in patients who have undergone carotid endarterectomy. Carotid endarterectomy involves the surgical removal of plaque from the carotid artery. By scanning the excised plaques and comparing the images with histopathological reference, investigators have confirmed the ability of 117mSn-DOTA-Annexin V to accurately identify high-risk areas within the plaques. Additionally, aortic aneurysms were imaged and verified by CT scan, indicating multi-faceted potential for vascular imaging. Although no new results have been published recently, the evidence so far shows significant promise that this agent can revolutionise the follow-up of patients with a high cardiovascular risk profile.

Therapeutic Efficacy: Dissolving Plaques, Cancer, and Rheumatoid Arthritis

117mSn allows the conversion of electron transfer energy to surrounding tissues over very short distances, causing highly localised damage. If these tissues are predominantly macrophage-laden, pro-inflammatory, and apoptotic in nature, the radiation can initiate pathways leading to plaque stabilisation or even plaque regression. Early animal studies have suggested that targeted apoptosis of macrophages within plaque areas can reduce plaque size and vulnerability.

Cancer Therapy

Cancers often contain tumours with areas of necrosis or inflammation, as well as vascular abnormalities that expose phosphatidylserine. By harnessing this tumour environment’s unique features, Tin-117m DOTA-Annexin V can infiltrate and remain in malignant tissue. Once bound, the short-range radiation can damage tumour cells while sparing much of the surrounding healthy tissue. Although cancer therapies commonly involve external beam radiation or broad-spectrum chemotherapeutic agents, a selective theranostic approach offers the benefit of attacking tumours from within while simultaneously confirming treatment efficacy via imaging.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disorder characterised by chronic inflammation of the joints, leading to pain, swelling, and eventually bone erosion. Immune cells within the synovium may expose phosphatidylserine or other markers that facilitate Annexin V binding. Targeted therapy using Tin-117m DOTA-Annexin V could downregulate the inflammatory response by selectively irradiating hyperactive immune cells in the joint. This approach holds the potential to mitigate the systemic effects associated with more generalised treatments, such as steroids or immunosuppressants.

Prospects in Alzheimer’s Disease Therapy

Alzheimer’s disease pathology includes the accumulation of amyloid-beta plaques, tau protein tangles, and chronic neuroinflammation. Microglia, the resident immune cells in the brain, are known to become dysfunctional or activated during this process, contributing to neuronal damage. Ageing microglia can shift to a pro-inflammatory phenotype, accelerating the decline in cognitive function.

Tin-117m DOTA-Annexin V and Targeted Microglial Destruction

Preliminary research indicates that microglia expressing phosphatidylserine or related markers can be targeted by Annexin V in a manner similar to other tissue macrophages. If validated in further studies, the short-range conversion electrons from 117mSn could selectively deplete or modulate these harmful microglia. This targeted approach might reduce the neuroinflammation that aggravates Alzheimer’s disease. Although the concept is still under development, the implications of a therapy that halts or even reverses aspects of Alzheimer’s would be momentous, potentially turning Tin-117m DOTA-Annexin V into a blockbuster in the neurology sphere.

Ongoing Clinical Trials: Phase II and Beyond

Currently, Tin-117m DOTA-Annexin V is undergoing a Phase II clinical study that focuses on individuals with carotid artery disease requiring endarterectomy. During surgery, the plaque is removed, offering the unique possibility of correlating imaging findings with histopathological results. Such correlation helps establish the reliability of 117mSn-DOTA-Annexin V imaging and clarifies how effectively it identifies vulnerable regions.

Aortic Aneurysm Imaging

Aortic aneurysms—particularly in the abdominal region—pose a significant risk of rupture, leading to life-threatening complications. The agent’s ability to detect inflammatory changes and vulnerable zones within the aneurysmal wall has been confirmed by comparisons with CT scans. This is expected to aid clinicians in deciding whether or not to intervene surgically and in monitoring the evolution of the aneurysm over time.

Limited Availability of Recent Results

Although no new results have been released recently, the data from the Phase II trials so far have laid a solid foundation for the expanded use of Tin-117m DOTA-Annexin V. The next step is likely to include larger population studies to confirm both efficacy and safety in broader patient groups. Additionally, once proof-of-concept is established in the area of cardiovascular, further studies focusing on cancer, rheumatoid arthritis, and Alzheimer’s disease can be expanded.

Future Directions and Conclusion

One of the primary challenges for new radiopharmaceuticals is the balance between optimal therapeutic efficacy and minimal toxicity. Tailoring dose regimens may involve adjusting the specific activity of the radionuclide, modifying the frequency of administration, or combining therapy with immunomodulators. These strategies aim to amplify therapeutic outcomes while minimising side effects.

Expanding Theranostic Applications

Researchers are exploring a variety of ligands, chelators, and isotopes to expand the range of targetable conditions. Nevertheless, Tin-117m DOTA-Annexin V has already set a precedent: combining a well-understood, highly specific targeting molecule (Annexin V) with a radioisotope that provides both imaging and precise local therapy. This powerful duality suggests that the platform can be adapted to new targets beyond phosphatidylserine, opening avenues for future applications in various inflammatory and degenerative diseases.

Regulatory and Commercial Considerations

For a radiopharmaceutical to be widely available, it must gain approval from regulatory bodies such as the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom. Part of this approval process involves demonstrating consistent manufacturing quality, safety, and clinical efficacy in multicentre trials. Should Tin-117m DOTA-Annexin V continue to show promise in both the cardiovascular and neurological domains, commercial interest is likely to escalate. The prospect of a therapy that not only prevents strokes and heart attacks but may also offer new hope for Alzheimer’s disease underscores the strong market potential.

Conclusion

Tin-117m DOTA-Annexin V is a pioneering step forward in the field of theranostics. By integrating a targeted protein, Annexin V, with the unique radiochemical properties of Tin-117m, this agent has exhibited compelling imaging capabilities in identifying vulnerable plaques and possibly mitigating the progression of cardiovascular disease. Beyond the heart and vasculature, the scope of this technology appears to extend to oncology, where it could zero in on tumours and deliver localised therapy, and to rheumatoid arthritis, where immune cells are similarly vulnerable. Furthermore, the potential for Alzheimer’s disease therapy represents a bold and exciting frontier, with early research suggesting that ageing microglia could be selectively targeted to control neuroinflammation.

In practical terms, the ability to image and simultaneously treat diseased tissues could transform the way clinicians diagnose and follow their patients. 117mSn-DOTA-Annexin V might well become an indispensable tool not just for advanced imaging but for integrative patient management across multiple disease domains.

Nevertheless, a considerable amount of research, regulatory oversight, and commercial planning must still take place. The Phase II clinical trial findings will serve as a crucial benchmark, potentially paving the way for Phase III studies that measure the agent’s long-term efficacy, safety, and cost-effectiveness in large patient populations. If results continue to validate early promises, Tin-117m DOTA-Annexin V will stand at the forefront of a radical shift in medical imaging and therapy—one that does not merely see disease but intervenes to halt, revert, or manage it effectively.

As scientific understanding and clinical experience expand, we may be on the cusp of a new era in personalised medicine. The possibility of diagnosing a plaque in a vulnerable state and simultaneously deploying targeted radiation to stabilise or eradicate it is an achievement that would dramatically reduce the burden of cardiovascular disease. Similarly, selectively targeting tumours or pathological immune cells in rheumatoid arthritis could mitigate risks and improve patients’ quality of life. For neurodegenerative conditions like Alzheimer’s, the horizon remains wide open, and innovative agents like Tin-117m DOTA-Annexin V offer renewed optimism for effective treatments in the future.

By building on these advancements, clinicians, researchers, and pharmaceutical innovators have the opportunity to reshape how we approach some of the most deadly and debilitating diseases worldwide. We await further data with great anticipation, hopeful that the next steps in clinical development will confirm what the existing evidence suggests: that Tin-117m DOTA-Annexin V is not just a theoretical concept but a tangible breakthrough in therapy and diagnosis.

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