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.
| Agent | Target | Isotope / Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Ac-225-DOTA-SP (Substance P) | Substance P (NK-1 receptor) | 225Ac–DOTA-SP | Glioblastoma | In clinical development | Alpha therapy for aggressive brain tumours |
| Ac-225-DOTA-YS5 | CD46 (prostate cancer) | 225Ac–IgG1 antibody | Prostate Cancer | Early stage | Potential targeted alpha therapy for advanced disease |
| Ac-225-DOTATOC | Somatostatin receptors | 225Ac–Edotreotide | Neuroendocrine Tumour (NET) | Early stage | Alpha-emitting alternative to beta therapies (e.g., Lu-177) |
| Ac-225-DOTAZOL | Bones | 225Ac–DOTAZOL | Bone pain palliation | Early stage | Addresses metastatic bone pain via alpha emission |
| Ac-225-FPI-1434 | IGF-1R | 225Ac–FPI-1434 | Solid Tumours | In clinical development | Alpha-based approach for IGF-1R-expressing malignancies |
| Ac-225-FPI-2059 | NTSR1 | 225Ac–3BP-227 | Solid Tumours | Early stage | Explores targeting neurotensin receptors in various cancers |
| Ac-225-FPI-2068 | EGFR | 225Ac–Fab | Solid Tumours | Early stage | EGFR targeting for multiple tumour types |
| Ac-225-FPI-2265 | PSMA | 225Ac–PSMA-I&T | Prostate Cancer | In clinical development | Alpha therapy directed at prostate-specific membrane antigen |
| Ac-225-Lintuzumab (Ac-225 Actimab-A™) | CD33 | 225Ac–Lintuzumab | AML, Colon cancer | In clinical development | Investigated mainly for AML but with potential in other cancers |
| Ac-225-MTI-201 | MCR1 (Melanocortin-1) | 225Ac–Fab | Uveal Cancer | Early stage | Targets melanocortin receptor in ocular melanoma |
| Ac-225-PSMA-617 | PSMA | 225Ac–Vipivotide | Prostate Cancer | In clinical development | Adds alpha power to PSMA-targeted therapy |
| Ac-225-Rosopatamab | PSMA | 225Ac–CONV-01-α | Prostate Cancer | In clinical development | Another alpha-based PSMA-targeting option |
| Ac-225-RYZ101 | Somatostatin receptors | 225Ac–Edotreotate | Solid Tumours | In clinical development | Alpha approach for tumours overexpressing these receptors |
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.
| Agent | Target | Isotope | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| At-211-81C6 | Tenascin (brain cancers) | 211At–81C6 | Brain Cancer | On hold or discontinued | Explored in high-grade glioma post-surgery |
| At-211-BC8-B10 | CD45 | 211At–BC8 | Acute leukaemia, AML, MDS | Early stage | Possible conditioning agent in stem cell transplant |
| At-211-MABG | Adrenergic tissues | 211At | Paragangliomas, Pheochromocytoma | In clinical development | Alpha alternative to I-131-MIBG |
| At-211-MX35-F(ab’)-2 | OVCAR-3 (ovarian) | 211At–MX35-F(ab’)2 | Ovarian Cancer | On hold or discontinued | Investigated for intraperitoneal therapy |
| At-211-NaAt | Thyroid tissues | 211At–NaAt | Thyroid Cancer | In clinical development | Harnesses astatine’s chemical similarity to iodine |
| At-211-Parthanatine | PARP1 | 211At–Peptide | Neuroblastoma | Early stage | Tests PARP1 inhibition strategy for paediatric tumours |
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.
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Bi-213-DOTATOC | SSTR | 213Bi–Edotreotide | NET | Early stage | Alpha therapy for somatostatin receptor-positive tumours |
| Bi-213-Lintuzumab (Bi-213) | CD33 | 213Bi–Lintuzumab | NHL | On hold or discontinued | Studied in CD33+ lymphomas |
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.
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Cu-64-Diasparagine CuASP | DNA | 64Cu | Brain Cancer | On hold or discontinued | Investigated for brain tumours |
| Cu-67-SAR-bisPSMA | PSMA | 67Cu–PSMA | Prostate Cancer | Early stage | A beta-emitter copper-based therapy |
| Cu-67-SARTATE | SSTR | 67Cu | Meningioma, Neuroblastoma, NET | In clinical development | Alternative to Lu-177 for SSTR-positive tumours |
Er-169 (Erbium-169) Radiopharmaceutical
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Er-169-Erbium Citrate | Brachytherapy (joints) | 169Er | Rheumatology | Marketed | Used for radiosynoviorthesis |
Ho-166 (Holmium-166) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Ho-166-Microspheres | Brachytherapy (liver) | 166Ho microspheres | Hepatocarcinoma | Marketed | Locoregional therapy for liver tumours |
| Ho-166-Chitosan | Brachytherapy (various) | 166Ho–chitosan | HCC,Melanoma, Prostate Cancer, Rheumatology, Tumours | Marketed | Flexible agent for intratumoural or intracavitary use |
| Ho-166-Phytate | Brachytherapy (joints) | 166Ho–phytate | Rheumatology | On hold or discontinued | Explored for radiosynoviorthesis |
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
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Lu-177-AMTG | GRPR | 177Lu–Bombesin | Prostate Cancer | Early stage | Explores alternative to PSMA targeting in prostate cancer |
| Lu-177-CTT-1403 | PSMA | 177Lu–CTT-1403 | Prostate Cancer | In clinical development | Continues the Lutetium PSMA therapy approach |
| Lu-177-Debio-1124 | CCK2R | 177Lu–Minigastrin PSIG-2 | Thyroid Cancer | On hold or discontinued | Explored for medullary thyroid carcinoma |
| Lu-177-DOTA-EB-FAPi | FAP (Fibroblasts) | 177Lu–FAPi | Solid Tumours, Thyroid Cancer | Early stage | Targets fibroblast activation protein in stromal components |
| Lu-177-DOTA-EB-TATE | SSTR | 177Lu–EB-TATE | NET, Head and Neck Cancer, Thyroid Cancer | In clinical development | Modified version of Lu-177-DOTATATE for improved pharmacokinetics |
| Lu-177-DOTAZOL | Bones | 177Lu | Pain palliation, Prostate Cancer | In clinical development | Similar to bisphosphonate-based approaches for bone metastases |
| Lu-177-DPI-4452 | CAIX | 177Lu–DPI-4452 | Colorectal, Pancreatic, Renal Cancers | Early stage | Targets hypoxic tumour marker CAIX |
| Lu-177-DTPA-Omburtamab | n/a | 177Lu–Omburtamab | Brain Cancer, Medulloblastoma | In clinical development | Potential intrathecal therapy for CNS tumours |
| Lu-177-EB-PSMA-617 | PSMA | 177Lu–EB-PSMA-617 | Prostate Cancer | In clinical development | Designed to enhance tumour uptake and retention |
| Lu-177-Edotreotide®) | SSTR | 77Lu–Edotreotide | NET | In clinical development | Similar to Lu-177-DOTATATE |
| Lu-177-EDTMP | Bones | 177Lu–EDTMP | Bone pain palliation | Marketed | Alleviates metastatic bone pain |
| Lu-177-FAP-2286 | FAP (Fibroblasts) | 177Lu–FAP-2286 | Solid Tumours | In clinical development | Another stroma-targeting radioligand |
| Lu-177-FAPI-04 | FAP (Fibroblasts) | 77Lu–FAPI-04 | Solid Tumours | Early stage | Investigates tumour stroma targeting |
| Lu-177-HTK03170 | PSMA | 177Lu–PSMA | Prostate Cancer | Early stage | Further refinement of PSMA-targeted Lutetium therapy |
| Lu-177-IPN-01087 | NTSR1 | 177Lu–IPN-01087 | Pancreatic Cancer | In clinical development | Targets neurotensin receptors common in pancreatic malignancies |
| Lu-177-iPSMA | PSMA | 177Lu–iPSMA | Prostate Cancer | Early stage | Seeks enhanced binding affinity for improved tumour retention |
| Lu-177-ITM-31 | CA XII | 177Lu–Fab | Glioblastoma | Early stage | Investigates carbonic anhydrase targeting in gliomas |
| Lu-177-Lilotomab (Satetraxetan Betalutin) | CD37 | 177Lu (unspecified) | NHL | On hold or discontinued | Formerly researched for B-cell malignancies |
| Lu-177-LNC1004 | FAP (Fibroblasts) | 177Lu–FAPi | Solid Tumours | Early stage | Part of the new wave of fibroblast-aimed treatments |
| Lu-177-LNC1010 | SSTR | 177Lu–Peptide | NET | Early stage | Another Lu-177 somatostatin analogue |
| Lu-177-Ludotadipep | PSMA | 177Lu–PSMA | Prostate Cancer | Early stage | Expands the list of PSMA-targeted Lutetium therapies |
| Lu-177-MVT-1075 | sLea | 177Lu–MVT-1075 | Pancreatic Cancer | In clinical development | Targets a carbohydrate antigen overexpressed in pancreatic tumours |
| Lu-177-Oxodotreotide (Lutathera®) | SSTR | 177Lu–Oxodotreotide | NET | Marketed | First-in-class Lu-177 peptide receptor radionuclide therapy |
| Lu-177-Pentixather | CXCR4 | 177Lu–Pentixather | Multiple Myeloma, Solid Tumours | In clinical development | Addresses the CXCR4 chemokine receptor pathway |
| Lu-177-PNT2002 | PSMA | 177Lu–PSMA-I&T | Prostate Cancer | In clinical development | Similar to other Lu-177–PSMA agents |
| Lu-177-PNT6555 | FAP (Fibroblasts) | 177Lu–FAPi | Solid Tumours | Early stage | Broad FAP-targeted strategy for various solid tumours |
| Lu-177-PSMA-ALB-56 | PSMA | 177Lu–PSMA-ALB-56 | Prostate Cancer | Early stage | Includes albumin-binding domain for enhanced tumour uptake |
| Lu-177-PSMA-R2 | PSMA | 177Lu–PSMA-R2 | Prostate Cancer | In clinical development | Next-generation PSMA radioligand therapy |
| Lu-177-rhPSMA-10.1 | PSMA | 177Lu–PSMA | Prostate Cancer | In clinical development | Another PSMA-targeted beta therapy |
| Lu-177-Rituximab | CD20 | 177Lu–Rituximab | NHL | Early stage | Radiolabelled version of a well-known anti-CD20 antibody |
| Lu-177-RM2 | GRPR | 177Lu–Bombesin | Prostate Cancer | In clinical development | Aims at a different prostate tumour marker |
| Lu-177-Rosopatamab | PSMA | 177Lu–Rosopatamab | Prostate Cancer | In clinical development | Beta counterpart to Ac-225-Rosopatamab |
| Lu-177-Satoreotide tetraxetan | SSTR | 177Lu–Satoreotide | NET | In clinical development | Similar in principle to Lutathera® |
| Lu-177-ST2210 (IART – Lu-177 DOTA-Biotin) | Avidin (pre-targeting) | 177Lu–Biotin | Breast cancer, Colon cancer | On hold or discontinued | Multi-step approach using tumour pre-targeting followed by radiolabelled biotin |
| Lu-177-TLX250 | CAIX | 177Lu–Girentuximab | Kidney Cancer | In clinical development | Targets CAIX in renal cell carcinoma |
| Lu-177-Vipivotide tetraxetan (Pluvicto™) | PSMA | 177Lu–Vipivotide | Prostate Cancer | Marketed | A leading radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC) |
| Lu-177-XT033 | PSMA | 177Lu–Peptide | Prostate Cancer | Early stage | An emerging PSMA-targeted candidate |
P-32 (Phosphorus-32) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| P-32-Colloidal Chromic Phosphate | Bones/brachytherapy | 32P | Brain Cancer, Rheumatology, Solid Tumours | Marketed | Used in intracavitary instillation or bone marrow ablation |
| P-32-OncoSil | Brachytherapy (pancreas) | 32P | Pancreatic Cancer | Marketed | Implant delivering localised beta radiation |
| P-32-Sodium Phosphate | Bones/myeloproliferative | 32P | Bone pain palliation, Polycythaemia vera | Marketed | Historical use for myeloproliferative disorders |
Pb-212 (Lead-212) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Pb-212-ADVC001 | PSMA | 212Pb–Peptide | Prostate Cancer | Early stage | Utilises alpha emission from Bi-212 decay |
| Pb-212-DOTAMTATE | SSTR | 212Pb–Dotamtate | NET | In clinical development | Alpha generator approach for somatostatin receptor-positive tumours |
| Pb-212-GRPR | GRPR | 212Pb–Bombesin | Solid Tumours | Early stage | Bombesin-based vector for GRPR-positive cancers |
| Pb-212-VMT-α-NET | SSTR | 212Pb–Peptide | NET | Early stage | Another alpha therapy for SSTR-positive tumours |
| Pb-212-VMT01 | MCR1 (Melanocortin-1) | 212Pb–VMT01 | Melanoma | Early stage | Evaluates alpha therapy in MCR1-positive melanoma |
Ra-223 (Radium-223) & Ra-224 (Radium-224)
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Ra-224-Radium Chloride (224-SpondylAT®) | Brachytherapy approach | 224Ra | Ankylosing Spondylitis | On hold or discontinued | Historically tested for inflammatory conditions |
| Ra-223-Radium Dichloride | Bones (calcium mimetic) | 223Ra | Bone pain palliation | Marketed | Known commercially as Xofigo® for prostate cancer bone metastases |
| Ra-224-RadSpherin | Brachytherapy spheres | 224Ra | Colon cancer, Ovarian Cancer | In clinical development | Localised alpha therapy for peritoneal or cavity-based malignancies |
Re-186 (Rhenium-186) & Re-188 (Rhenium-188) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Re-188-Etidronate (HEDP) | Bones, Rheumatology | 188Re–HEDP | Bone pain palliation, Rheumatology | Marketed | Similar to Re-186-HEDP but uses the Re-188 isotope |
| Re-186-Rhenium Etidronate (HEDP) | Bones | 186Re–HEDP | Bone pain palliation | Marketed | Beta therapy for metastatic bone lesions |
| Re-186-RNL | Brachytherapy (brain) | 186Re–(RNL) | Glioblastoma | In clinical development | Intratumoural injection approach for brain tumours |
| Re-188-Dendrimer (ImDendrim) | Brachytherapy (HCC) | 188Re–Dendrimer | Hepatocarcinoma | Early stage | Nanocarrier-based therapy delivered to liver tumours |
| Re-188-Rhenium Lipiodol | Fatty acids (liver) | 188Re–Lipiodol | Hepatocarcinoma | Marketed | Analogous to I-131-Lipiodol for selective internal radiation |
| Re-188-SSS/Lipiodol | Fatty acids (liver) | 188Re–Lipiodol variant | Liver cancer | In clinical development | Another locoregional therapy for hepatocellular carcinoma |
| Re-188-P2045 (Tozaride) | SSTR | 188Re–Tozaride | Lung Cancer, Pancreatic Cancer | In clinical development | Beta therapy aimed at somatostatin receptor-positive tumours |
| Re-188-Rhenium Skin Cancer Therapy | Brachytherapy (skin) | 188Re | Non-Melanoma skin cancer | Marketed | Delivers beta radiation to superficial lesions |
| Re-186-Rhenium Sulfide | Brachytherapy | 186Re–Sulfide | Rheumatology | Marketed | Used in radiosynoviorthesis |
| Re-188-Rhenium Sulfide | Brachytherapy | 188Re–Sulfide | Rheumatology | Marketed | Similar usage as Re-186-Sulfide in joint inflammation |
Sm-153 (Samarium-153) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Sm-153-DOTMP (CycloSAM) | Bones | 153Sm–DOTMP | Bone pain palliation | In clinical development | Targets skeletal metastases |
| Sm-153-Lexidronam (EDTMP) | Bones | 153Sm–EDTMP | Bone pain palliation | Marketed | Known commercially as Quadramet™, widely used for bone metastases |
| Sm-153-Oxabiphor (ETMP) | Bones | 153Sm–ETMP | Bone pain palliation | Marketed | Another variant for palliative treatment of bone metastases |
Sn-117m (Tin-117m) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Sn-117m-DOTA-Annexin-V | Annexin-V | 117mSn–Annexin-V | Rheumatology, Vulnerable plaque | In clinical development | Conversion electron emitter for inflamed joints or atherosclerotic plaques |
| Sn-117m-DTPA | Bones | 117mSn–DTPA | Bone pain palliation | In clinical development | Potential alternative to standard beta emitters for palliative bone treatments |
| Sn-117m-HTC (Synovetin) | Brachytherapy (joints) | 117mSn | Rheumatology | Marketed | Used in radiosynoviorthesis to reduce chronic inflammation in joints |
Sr-89 (Strontium-89) Radiopharmaceutical
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Sr-89-Strontium Chloride | Bones (calcium mimic) | 89Sr | Bone pain palliation | Well-known therapy for painful bone metastases |
Tb-161 (Terbium-161) Radiopharmaceutical
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Tb-161-PSMA-I&T | PSMA | 161Tb–PSMA-I&T | Prostate Cancer | Early stage | Investigates terbium’s beta/Auger electron emission for improved control |
Th-227 (Thorium-227) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Th-227-Anetumab corixetan | Mesothelin | 227Th–Anetumab | Ovarian Cancer, Solid Tumours | Early stage | Utilises alpha emission for mesothelin-overexpressing tumours |
| Th-227-Epratuzumab (Th-227-BAY1862864) | CD22 | 227Th–Epratuzumab | NHL | On hold or discontinued | Explored alpha-based therapy against B-cell malignancies |
| Th-227-Pelgifatamab | PSMA | 227Th–PSMA antibody | Prostate Cancer | Early stage | Another alpha emitter targeting prostate-specific membrane antigen |
Y-90 (Yttrium-90) Radiopharmaceuticals
| Agent | Target | Isotope/Payload | Indication(s) | Clinical Status | Remarks |
|---|---|---|---|---|---|
| Y-90-Anditixafortide | CXCR4 | 90Y–Pentixather | Multiple Myeloma, Solid Tumours | In clinical development | Similar concept to Lu-177-Pentixather, using a higher-energy beta emitter |
| Y-90-Basixilimab | CD25 (IL-2R) | 90Y–Basixilimab | Hodgkin’s Lymphoma, NHL | In clinical development | Targets activated T-cells in lymphoma microenvironment |
| Y-90-Besilesomab | CD66 | 90Y–Besilesomab | Amyloidosis | In clinical development | Investigated for treating amyloid deposits |
| Y-90-Betaglue | Brachytherapy | 90Y–resin/gel | Breast cancer, HCC, Solid Tumours | In clinical development | A patch or gel delivering localised beta radiation |
| Y-90-Carbon Microspheres | Brachytherapy | 90Y–microspheres | Hepatocarcinoma | In clinical development | Similar principle to resin/glass Y-90 microspheres (e.g., SIR-Spheres®) |
| Y-90-Daclizumab (HAT) | CD25 | 90Y–Daclizumab | Leukaemia, NHL | On hold or discontinued | Previously tested in haematological malignancies |
| Y-90-DOTA-FF-21101 | IGF-1R / p-cadherin? | 90Y–p-cadherin | Biliary Tract, Head and Neck, Ovarian Cancers | Early stage | Targets tumour growth pathways (some data mismatch in sources) |
| Y-90-DOTALAN (Lanreotide) | SSTR | 90Y–Lanreotide | NET | On hold or discontinued | Early approach preceding more common Lu-177 analogues |
| Y-90-DOTATOC (Edotreotide) | SSTR | 90Y–Edotreotide | NET | On hold or discontinued | Pioneered peptide receptor radionuclide therapy prior to Lu-177 versions |
| Y-90-Epratuzumab Tetratexan | CD22 | 90Y–Epratuzumab | NHL | On hold or discontinued | Explored radioimmunotherapy against CD22+ B-cells |
| Y-90-FAPI-04 | FAP | 90Y–FAPI-04 | Solid Tumours | Early stage | Beta-emitting stroma-targeting therapy |
| Y-90-FAPI-46 | FAP | 90Y–FAPI-46 | Tumour growth | In clinical development | Part of the expanding FAP-targeted portfolio |
| Y-90-Ferritarg | Ferritin | 90Y–Ferritarg | Hodgkin’s Lymphoma | On hold or discontinued | Targeted tumour-associated ferritin for HL |
| Y-90-Ibritumomab Tiuxetan | (Listed as IGF-1R) | 90Y–Ibritumomab | Biliary Tract, Head & Neck, Ovarian Cancers (preclinical) | Preclinical | CD20-targeted (Zevalin®) for lymphoma; possibly a new research direction indicated |
| Y-90-IsoPet – Y-90-RadioGel | Brachytherapy | 90Y | Solid Tumours | Marketed | Injectable gel for localised radiation (veterinary and potential human use) |
| Y-90-Microspheres | Brachytherapy | 90Y–microspheres | Hepatocarcinoma | Marketed | Commercial resin/glass microsphere products (e.g., SIR-Spheres®, TheraSphere®) |
| Y-90-OPS201 (SOMTher®) | SSTR | 90Y–OPS201 | NET | On hold or discontinued | Used for radiosynoviorthesis, like Er-169 or Re-186, in joint diseases |
| Y-90-Tabituximab barzuxetan | FZD10 | 90Y–OTSA101 | Synovial sarcoma | Early stage | Investigates Wnt signalling receptor in this rare malignancy |
| Y-90-Yttrium Citrate | Rheumatology | 90Y–citrate | Rheumatology | Marketed | Used for radiosynoviorthesis, like Er-169 or Re-186 in joint diseases |
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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