ABSTRACT
With the discovery of radioiodine therapy, whose origins date back to 1936, targeted therapeutic applications have become one of the cornerstones of nuclear medicine. In recent decades, the discovery of numerous molecules labelled with other beta-emitting radionuclides such as Lu-177 and Y-90 has ensured rapid progress in this field. The success of beta-emitting radiopharmaceuticals has focused attention on treatment with alpha radionuclides. Targeted alpha radionuclide therapies offer a more effective treatment option due to their high linear energy transfer, while their short range limits the impact on healthy tissue and thus the potential side effects. For these reasons, alpha radionuclide therapies hold great promise in cancer treatment. This review briefly summarises the ongoing phase studies on alpha radionuclide therapy.
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1
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Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC https://clinicaltrials.gov/ct2/show/NCT04506567
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ACTInium-J591 Radionuclide Therapy in PSMA-Detected Metastatic HOrmone-Sensitive Recurrent Prostate CaNcer (ACTION) https://clinicaltrials.gov/ct2/show/NCT05567770
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Maximizing Responses to Anti-PD1 Immunotherapy With PSMA-targeted Alpha Therapy in mCRPC https://clinicaltrials.gov/ct2/show/NCT04946370
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Dose Escalation and Efficacy Study of 212Pb-ADVC001 in Patients With Metastatic Castration Resistant Prostate Cancer https://clinicaltrials.gov/ct2/show/NCT05720130
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Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer https://clinicaltrials.gov/ct2/show/NCT03724747
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Study of RYZ101 Compared With SOC in Pts With Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy https://clinicaltrials.gov/ct2/show/NCT05477576
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Study of RYZ101 in Combination With SoC in Subjects With SSTR+ ES-SCLC https://clinicaltrials.gov/ct2/show/NCT05595460
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Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors (212-Pb-VMT) https://clinicaltrials.gov/ct2/show/NCT05636618
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Targeted Alpha-emitter Therapy of PRRT Naive Neuroendocrine Tumor Patients (ALPHAMEDIX02) https://clinicaltrials.gov/ct2/show/NCT05153772
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A Safety Study of 212Pb-Pentixather Radioligand Therapy https://clinicaltrials.gov/ct2/show/NCT05557708
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Venetoclax and Lintuzumab-Ac225 in AML Patients https://clinicaltrials.gov/ct2/show/NCT03867682
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Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients https://clinicaltrials.gov/ct2/show/NCT03932318
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Lintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia https://clinicaltrials.gov/ct2/show/study/NCT03441048
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211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia https://clinicaltrials.gov/ct2/show/NCT03128034
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211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome https://clinicaltrials.gov/ct2/show/NCT03670966
19
Total Body Irradiation and Astatine-211-Labeled BC8-B10 Monoclonal Antibody for the Treatment of Nonmalignant Diseases https://clinicaltrials.gov/ct2/show/NCT04083183
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Radioimmunotherapy (211At-OKT10-B10) and Chemotherapy (Melphalan) Before Stem Cell Transplantation for the Treatment of Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04466475
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211At-OKT10-B10 and Fludarabine Alone or in Combination With Cyclophosphamide and Low-Dose TBI Before Donor Stem Cell Transplant for the Treatment of Newly Diagnosed, Recurrent, or Refractory High-Risk Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04579523
22
Radioimmunotherapy (111Indium/225Actinium-DOTA-daratumumab) for the Treatment of Relapsed/Refractory Multiple Myelom https://clinicaltrials.gov/ct2/show/NCT05363111
23
MC1R-targeted Alpha-particle Therapy Trial in Adults With Advanced Melanoma https://clinicaltrials.gov/ct2/show/NCT05655312
24
Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma https://clinicaltrials.gov/ct2/show/NCT05496686
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Actinium 225 Labeled Anti-CEA Antibody (Ac225-DOTA-M5A) for the Treatment of CEA Producing Advanced or Metastatic Cancers https://clinicaltrials.gov/ct2/show/NCT05204147
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A Study of [225Ac]-FPI-2059 in Adult Participants With Solid Tumours https://clinicaltrials.gov/ct2/show/NCT05605522
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A Phase 1/2 Study of [225Ac]-FPI-1434 Injection https://clinicaltrials.gov/ct2/show/NCT03746431
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A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours https://clinicaltrials.gov/ct2/show/NCT05363605
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A First in Human Study of BAY2701439 to Look at Safety, How the Body Absorbs, Distributes and Excretes the Drug, and How Well the Drug Works in Participants With Advanced Cancer Expressing the HER2 Protein https://clinicaltrials.gov/ct2/show/NCT04147819
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Safety and Tolerability of ²¹²Pb-DOTAM-GRPR1 ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors https://clinicaltrials.gov/ct2/show/NCT05283330