Summary: Radiopharmaceuticals represent a fascinating intersection of nuclear physics, chemistry, and clinical oncology. These subjects combine radioactive isotopes with targeting molecules, allowing them to localise within tumours and deliver cytotoxic radiation directly to malignant cells. This targeted approach makes it possible to reduce off-target effects on healthy tissues and achieve therapeutic outcomes that might not be feasible with conventional chemotherapies or external beam radiation. The tables below present a detailed catalogue of these radionuclides, spanning alpha, beta, and conversion electron emitters, each with its targeting mechanism, clinical status, and specific cancer indication. Below is an in-depth exploration of the main categories outlined in the tables and a final summary highlighting the significance of radiopharmaceuticals in modern medicine.
Introduction
Radiopharmaceuticals can be broadly classified by the radioisotope they employ. Alpha emitters such as Actinium-225 (Ac-225) and Astatine-211 (At-211) produce high-energy, short-path radiation. This powerful emission is highly effective in destroying tumour cells, with minimal penetration into surrounding healthy tissue. Beta emitters, including Lutetium-177 (Lu-177), Iodine-131 (I-131), Yttrium-90 (Y-90), and others, offer deeper tissue penetration and are often used both in tumour therapy and bone pain palliation. Conversion electron emitters, such as Tin-117m (Sn-117m), harness distinctive radiation profiles suitable for specific conditions like rheumatoid arthritis or atherosclerotic plaques. Each entry in the tables details a radionuclide target (e.g., a receptor or antigen), clinical status, and a brief note on why it might be clinically promising or, conversely, why it has been discontinued.
These tables encompass well-established treatments, such as I-131 for thyroid cancer and Ra-223 for bone metastases, as well as investigational radionuclides still at the frontier of clinical research. Below, you will find the main highlights from each section of the table.
Iodine-131 is arguably the most established beta-emitting radionuclide in therapeutic nuclear medicine. I-131-Sodium Iodide has been a mainstay for treating thyroid cancer for decades, leveraging the thyroid gland’s ability to concentrate iodine from the bloodstream. Furthermore, agents like I-131-Iobenguane (MIBG) target adrenergic tissues and have offered novel approaches to neuroblastoma and pheochromocytoma. Within the table, you will also find I-131-Lipiodol for hepatocarcinoma, as well as I-131-RPS-001, which targets PSMA in prostate cancer.
Beyond iodine, the table includes beta emitters such as Lutetium-177, Yttrium-90, Rhenium-186/188, Samarium-153, and more. Lu-177-Oxodotreotide (Lutathera®), for example, gained approval for neuroendocrine tumours of gastrointestinal origin, demonstrating a favourable safety profile compared with some older treatments. Y-90-Microspheres (e.g., SIR-Spheres® or TheraSphere®) have become a standard therapy for liver tumours, delivering high-dose radiation directly to hepatic lesions while sparing most healthy liver tissue.
Alpha vs Beta Emission: Clinical Considerations
Alpha emitters, including Ac-225, At-211, Th-227, and Pb-212, release highly energetic alpha particles that travel only a few cell diameters. This produces intense local damage, which is excellent for eradicating small clusters of tumour cells and micrometastases. However, the short path length can limit larger masses, and ensuring the isotope remains stably chelated during circulation is essential.
Beta emitters, such as Lu-177, I-131, Y-90, and Re-186, have less energetic but more penetrating emissions. This characteristic can be advantageous for larger tumours, as the radiation can reach tumour cells situated further away from blood vessels. Each approach has trade-offs, making the choice of radionuclide highly dependent on the tumour type, size, and location, as well as patient-specific factors.
Clinical Development, Marketed Products, and Discontinuations
From the table, it is clear that some agents have been discontinued while others have progressed to marketing. I-131-Sodium Iodide, Ra-223 Radium Dichloride, and Lu-177-Oxodotreotide (Lutathera®) stand out as examples of successfully marketed radiopharmaceuticals. They have transformed the management of thyroid cancer, bone metastases in prostate cancer, and neuroendocrine tumours, respectively.
Conversely, some agents are indicated as “on hold or discontinued,” reflecting the ongoing evolution of clinical research. Developing radiopharmaceuticals is a costly and technologically challenging enterprise that supply constraints, manufacturing hurdles, and insufficient therapeutic indices in clinical trials can hinder. Nevertheless, each setback can provide valuable data that guide future innovation.
Ac-225 (Actinium-225) Radiopharmaceuticals
In the table below, Ac-225-based therapies stand out for their alpha-emission profile, which releases intense, short-range ionising particles. Examples include Ac-225-DOTA-SP (Substance P) for glioblastoma and Ac-225-PSMA-617 for prostate cancer. These agents rely on an intricate balance of chemical stability and tumour-specific ligands, ensuring that the radioactive isotope remains attached while it travels through the bloodstream. Once the radiopharmaceutical reaches its target, the alpha particles can produce double-strand DNA breaks in tumour cells, often leading to cell death.
Certain Ac-225 programmes, such as Ac-225-Lintuzumab (Actimab-A™), target CD33 in acute myeloid leukaemia (AML). This approach attempts to achieve a more precise delivery of alpha radiation to malignant blasts while sparing normal haematopoietic cells as much as possible. Another noteworthy category is the PSMA-targeted Ac-225 agents, specifically designed for advanced prostate cancer. By binding to the prostate-specific membrane antigen, these radiopharmaceuticals concentrate radioactive payloads in metastatic lesions and can shrink or stabilise otherwise treatment-resistant disease.
At-211 (Astatine-211) Radiopharmaceuticals
Astatine-211 is another alpha emitter with a half-life that often suits localised administration. Agents like At-211-81C6 (Neuradiab) and At-211-MX35-F(ab’)-2 have been investigated for brain cancer and ovarian cancer, respectively. Here, the idea is similar: deliver alpha particles directly to the tumour site so that the potent radiation can eradicate remaining malignancies. In some cases, trials have been put on hold or discontinued, highlighting the complexity of harnessing astatine, which has unique handling and production challenges. Nevertheless, At-211-NaAt remains an intriguing option for thyroid cancers due to astatine’s chemical similarity to iodine, potentially allowing it to be taken up by thyroid tissue in a manner similar to radioiodine treatments.
Bi-213 (Bismuth-213) Radiopharmaceuticals
Bismuth-213, another alpha emitter, is produced from decaying Actinium-225 generators. Agents such as Bi-213-DOTATOC, which targets somatostatin receptors, and Bi-213-Lintuzumab for CD33-expressing cells illustrate how alpha therapy continues to evolve. The short half-life of Bi-213 can be advantageous, reducing patients’ overall radiation exposure time. However, meticulous logistical planning is also required to ensure that treatments are administered rapidly after the isotope is generated. Research indicates that alpha therapies based on bismuth-213 can be extremely potent, though practical constraints have sometimes limited widespread adoption.
Cu-64 / Cu-67 (Copper) Radiopharmaceuticals
Several entries in the table reference copper-based therapies, such as Cu-67-SAR-bisPSMA, for prostate cancer. Copper isotopes are sometimes seen as emerging contenders in nuclear medicine because of their imaging and therapeutic potential, depending on whether Cu-64 or Cu-67 is used. This dual capability can aid personalised dosimetry and scheduling.
Meanwhile, tin-117m (Sn-117m) stands out among conversion electron emitters. Its radiation type is well suited for minimal tissue penetration, which can be beneficial in conditions like rheumatoid arthritis. Sn-117m-DOTA-Annexin-V and Sn-117m-HTC (Synovetin) are specifically developed for radiosynoviorthesis, reducing joint inflammation in a targeted manner.
Er-169 (Erbium-169) Radiopharmaceutical
Ho-166 (Holmium-166) Radiopharmaceuticals
I-131 (Iodine-131) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| I-131-81C6 mAb (Neuradiab™) | Tenascin | 131I–81C6 mAb | Brain Cancer | On hold or discontinued | Investigated in high-grade brain tumours |
| I-131-Apamistamab (Iomab-B™) | CD45 | 131I–Apamistamab | ALL, AML, HL, MDS, NHL | In clinical development | Conditioning regimen for bone marrow transplant |
| I-131-BA52 | Melanin | 131I–BA52 | Melanoma | On hold or discontinued | Explored for targeting melanin in melanoma |
| I-131-CAM-H2 | HER2 | 131I–SGMIB | Breast cancer | In clinical development | Targets HER2-positive disease |
| I-131-chTNT (Vivatuxin) | DNA | 131I–Derlotuximab | Brain Cancer, HCC, Lung Cancer | Marketed | Binds necrotic cores of tumours |
| I-131-ICF01012 | Melanin | 131I–ICF01012 | Melanoma | Early stage | Another melanin-targeting option for melanoma |
| I-131-IMAZA | Adrenergic tissues | 131I–Iobenguane | Adrenal cell carcinoma (ACC) | In clinical development | Similar to MIBG concept, aimed at ACC |
| I-131-Iobenguane (MIBG) | Adrenergic tissues | 131I–Iobenguane | Neuroblastoma, NET, Pheochromocytoma | Marketed | A mainstay in treating neuroendocrine tumours and neuroblastoma |
| I-131-Iopofosine | PI3K | 131I–CLR 131 | Multiple Myeloma | In clinical development | Investigated in haematological malignancies |
| I-131-Lipiodol | Fatty acids (liver) | 131I–Lipiodol | Hepatocarcinoma | Marketed | Selective internal radiation therapy for HCC |
| I-131-Metuximab | CD147 | 131I | Hepatocarcinoma | Marketed | Targets CD147 on HCC cells |
| I-131-Naxitamab | GD2 | 131I–Naxitamab | Neuroblastoma | In clinical development | Builds on GD2 targeting in paediatric solid tumours |
| I-131-Omburtamab | B7-H3/CD276 | 131I–Omburtamab | Neuroblastoma, Soft tissue cancer | In clinical development | Investigated for CNS or metastatic disease |
| I-131-RPS-001 | PSMA | 131I–RPS-001 | Prostate Cancer | In clinical development | Beta-emitter alternative to Lu-177–PSMA therapies |
| I-131-Sodium Iodide | Thyroid tissues | 131I–NaI | Thyroid Cancer, Head/Neck Cancer | Marketed | Widely used for thyroid cancer ablation |
| I-131-TLX-101 | LAT-1 | 131I–Phenylalanine | Brain Cancer | In clinical development | Exploits amino acid transporter upregulation |
| I-131-TM601 | Annexin | 131I–Chlorotoxin | Glioma, Melanoma | On hold or discontinued | Derived from scorpion toxin, once tested for tumour targeting |
| I-131-Tositumomab (Bexxar®) | CD20 | 131I–Tositumomab | NHL | On hold or discontinued | Previously FDA-approved; commercial availability ended |
| I-131-Weimeisheng | DNA | 131I–Weimeisheng | Lung Cancer | Marketed | Focuses on delivering radioiodine to malignant lung cells |
Lu-177 (Lutetium-177) Radiopharmaceuticals
P-32 (Phosphorus-32) Radiopharmaceuticals
Pb-212 (Lead-212) Radiopharmaceuticals
Ra-223 (Radium-223) & Ra-224 (Radium-224)
Re-186 (Rhenium-186) & Re-188 (Rhenium-188) Radiopharmaceuticals
Sm-153 (Samarium-153) Radiopharmaceuticals
Sn-117m (Tin-117m) Radiopharmaceuticals
Sr-89 (Strontium-89) Radiopharmaceutical
Tb-161 (Terbium-161) Radiopharmaceutical
Th-227 (Thorium-227) Radiopharmaceuticals
Y-90 (Yttrium-90) Radiopharmaceuticals
Conclusion
Radiopharmaceuticals hold a unique place in oncology, offering the promise of targeted therapies that spare healthy tissue while delivering lethal radiation to tumour cells. The tables above demonstrate the breadth of current and past initiatives, covering numerous isotopes, targets, and clinical trial outcomes. Whether alpha or beta emitters, each agent occupies a specific niche aligned with its physical properties, chemical behaviour, and tumour biology.
Although some programmes have not advanced beyond the early stages, many continue to drive the field forward, revealing new ways to harness radioisotopes for therapeutic gain. As research progresses, it is likely that newer agents will join the ranks of established therapies, and more patients will benefit from these targeted approaches.
- Range of Isotopes: The table includes alpha emitters like Ac-225, At-211, Pb-212, and Th-227, as well as beta emitters such as Lu-177, I-131, Y-90, Re-186/188, and Sm-153. Conversion electron emitters (Sn-117m) and copper isotopes (Cu-64/67) broaden the range of available radiation types.
- Targeted Mechanisms: Many radiopharmaceuticals exploit tumour-associated antigens or receptors, including PSMA (prostate cancer), somatostatin receptors (neuroendocrine tumours), CD33 (myeloid leukaemias), and fibroblast activation protein (various solid tumours).
- Clinical Variation: The radionuclides in the tables span the entire clinical pipeline, from early exploration to marketed products. Some older trials were discontinued, while others led to groundbreaking therapies like Ra-223 (bone metastases) and Lutathera® (NETs).
- Therapeutic Advantages: By carrying lethal radiation directly to the tumour, radiopharmaceuticals can achieve high tumour cell kill with minimal collateral damage. Alpha emitters excel at targeting small, localised clusters, while beta emitters work well against more extensive lesions. Each has advantages depending on the tumour context.
- Future Outlook: Ongoing developments in radiochemistry, chelation technology, and molecular biology suggest that radiopharmaceuticals will only grow in relevance. Personalised dosimetry, combined therapies (e.g., with immunotherapy), and more advanced manufacturing methods may soon expand the scope and success of these targeted treatments.
Therefore, these tables illustrate the dynamic landscape of radiopharmaceutical innovation. From early-stage experiments to fully approved therapies, it is evident that harnessing radioisotopes for cancer care has yielded notable achievements and holds vast potential for future breakthroughs. Researchers aim to refine these agents by carefully optimising targeting ligands, isotopes, and delivery methods, delivering powerful, precise, and patient-centred treatments in the ever-evolving battle against cancer.
Disclaimer
The content provided in “Radiopharmaceutical Innovation: An Overview for Targeted Therapy” is intended for informational and educational purposes only. It does not constitute medical advice, diagnostic guidance, or professional endorsement of any specific treatment or product. While every effort has been made to ensure the accuracy and currency of the information presented, the field of radiopharmaceuticals is rapidly evolving, and clinical data, regulatory approvals, and therapeutic indications may change over time.
This article should not be used as a substitute for professional judgement in clinical decision-making. Readers are encouraged to consult qualified healthcare professionals or relevant regulatory authorities for personalised medical advice or before initiating any course of treatment. The inclusion of agents in clinical development, or those that have been discontinued, does not imply recommendation or future approval. Any mention of commercial products, trade names, or manufacturers is for reference only and does not imply endorsement.
The authors and publishers disclaim all liability for any loss, injury, or damage incurred as a consequence of the use of information presented in this document.
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