Rhenium Radioisotopes for Medicine, a Focus on Production and Applications
Abstract
:1. Introduction
2. Rhenium-186 Nuclear Properties and Production
3. Rhenium-188 Nuclear Properties and Production
4. Chemistry of Rhenium Radiopharmaceuticals
5. 188/186 Re-Radiopharmaceuticals Clinical Application
5.1. “Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioma” and “Intraventricular Administration of 186Re-NanoLiposome for Leptomeningeal Metastases”
5.2. “Multicentre Canadian Study to Measure the Safety and Efficacy of Radiosynoviorthesis”
5.3. ”Rhenium-Skin Cancer Therapy (SCT) for the Treatment of Non-Melanoma Skin Cancer” (Phase IV, NCT05135052, Recruiting)
5.4. “Rhenium-188-HEDP vs. Radium-223-chloride in Patients with Advanced Prostate Cancer Refractory to Hormonal Therapy” (Phase III, NCT03458559, Active, Not Recruiting)
5.5. “Rhenium 188Re-P2045 in Small Cell Lung Cancer and Other Advanced Neuroendocrine Carcinoma” and “188Re-P2045 in Patients with Lung Cancer Who Have Received or Refused to Receive Prior Chemotherapy”
5.6. “188Re-SSS Lipiodol to Treat HepatoCellular Carcinomas” (NCT0112646, Phase I, Completed)
5.7. “HER2 Expression Detection and Radionuclide Therapy in Breast Cancer Using 99mTc/188Re Labeled Single Domain Antibody (NCT04674722, Phase I, Recruiting)
5.8. Treatment of Non-Responding to Conventional Therapy Inoperable Liver Cancers by in Situ Introduction of ImDendrim (NCT03255343)
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Eβ- [keV] (Int %) | EAuger e- [keV] (Int %) | Eγ [keV] (Int %) | EX-rays [keV] (Int %) | |
---|---|---|---|---|
186Re→186W | 6.53 (4.96%) | 122.64 (0.603%) | 8.4 (1.96%) | |
45.7 (0.29%) | 57.981 (1.72%) | |||
59.318 (2.95%) | ||||
Mean energy: | 1.3 (57%) | 122.64 (0.603%) | 46 (8.3%) | |
186Re→186Os | 306.1 (21.54%) | 6.88(6.55%) | 137.157 (9.47%) | 8.91(2.92%) |
359.2 (70.99%) | 48.3(0.179%) | 61.486 (1.14%) | ||
63.0 (1.94%) | ||||
Mean energy: | 346.7 (92.59%) | 1.3 (71%) | 106 (12.1%) | 38 (7.3%) |
Eβ- [keV] (Int %) | EAuger e- [keV] (Int %) | Eγ [keV] (Int %) | EX-rays [keV] (Int %) | |
---|---|---|---|---|
188Re→188Os | 527.779 (1.85%) | 6.88 (6.84%) | 155.044 (15.49%) | 8.91 (3.04%) |
728.88 (25.8%) | 48.3 (0.219%) | 478.00 (1.076%) | 61.486 (1.40%) | |
795.41 (70.7%) | 6.33.03 (1.370%) | 63.0 (2.38%) | ||
Mean energy: | 763 (100.2%) | 1.3 (75%) | 40.8 (8.4%) |
Reaction | E°Re [V] | E°Tc [V] | ΔE° [V] |
---|---|---|---|
MO4− + 3e− + 4H+ → MO2 + 2H2O | 0.51 | 0.74 | −0.23 |
MO4− + 7e− + 8H+ → M + 4H2O | 0.36 | 0.47 | −0.11 |
Actual Start/End Study Date and Status | Brief Title | Brief Summary | Study Phase | Condition | Drug/Device | Study Sponsor |
---|---|---|---|---|---|---|
January 2000/February 2001 Completed | Biodistribution Study With 186Re-labelled Humanised Monoclonal Antibody BIWA 4 in Patients With Adenocarcinoma of the Breast. NCT02204046 | To evaluate the safety and tolerability of 186Re-bivatuzumab administered intravenously (i.v.) and to study biodistribution and pharmacokinetics in patients with breast adenocarcinoma. | Phase I | Brest Adenocarcinoma | 186Re-labelled humanized monoclonal antibody BIWA 4 | Boehringer Ingelheim |
December 1999/February 2001 Completed | Biodistribution Study With 186Re-labelled Humanised Monoclonal Antibody BIWA 4 in Patients With Non-small Cell Lung Cancer NCT02204059 | To evaluate the safety and tolerability of 186Re-bivatuzumab administered intravenously (i.v.) and to study biodistribution and pharmacokinetics in patients with non-small cell lung cancer (NSCLC). | Phase I | Carcinoma, Non-Small-Cell Lung | 186Re-labelled humanized monoclonal antibody BIWA 4 | Boehringer Ingelheim |
March 1999/June 2001 Completed | Dose Escalation Study With 99mTC—or 186 Re-labelled Humanised Monoclonal Antibody (hMAb) BIWA 4 in Patients With Head and Neck Cancer. NCT02204033 | To evaluate the safety and tolerability of 186Re-bivatuzumab administered intravenously (i.v.) and to study biodistribution and pharmacokinetics in patients with Head and Neck Neoplasms. | Phase I | Head and Neck Neoplasms | 186Re-labelled humanized monoclonal antibody BIWA 4 | Boehringer Ingelheim |
April 2006/April 2007 Completed | Identification of Sentinel Lymph Nodes With Methylene Blue and Isotope NCT00314405 | To evaluate the performance of a double labeling method using isotope and methylene blue dye injection to localize precisely Sentinel Lymph Node (SLN) in a series of 100 patients with infiltrative breast cancer justifying SLN excision. | NA | Infiltrative Breast Cancer | 186Re-Sulfide (Device) | University Hospital, Strasbourg, France |
31 May 2012/31 December 2018 Completed | Multicentre Canadian Study to Measure the Safety and Efficacy of Radiosynoviorthesis NCT01615991 | Multicentre Canadian Study to Measure the Safety and Efficacy of Synoviorthesis Performed With 90Y- or 186Re-Sulfide. | Phase III | Arthritis or chronic inflammatory joint disease. | 186Re-Sulfide | Centre de recherche du Centre hospitalier universitaire de Sherbrooke |
3 June 2015/January 2025 Recruiting | Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioma (ReSPECT). NCT01906385 | Volume and dose escalation study of the safety, tolerability, and distribution of 186RNL in patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment. | Phase I; Phase II | Glioma. | 186Re-NanoLiposomes (186RNL) | Plus Therapeutics |
6 December 2021/30 December 2022 Recruiting | Intraventricular Administration of 186Re-NanoLiposome for Leptomeningeal Metastases NCT05034497 | An open-label Phase I clinical study that will administer a single dose of 186RNL via intraventricular catheter for the treatment of Leptomeningeal Metastases (LM). | Phase I | Leptomeningeal Metastasis | 186Re-NanoLiposomes (186RNL) | Plus Therapeutics |
26 May 2010/6 August 2019 Completed | 188Re-SSS Lipiodol to Treat HepatoCellular Carcinomas NCT01126463 | To determine the maximum tolerated dose and the recommended 188Re-SSS Lipiodol activity for hepatic intra-arterial injection in patients with hepato-cellular carcinoma. | Phase I | Hepatocellular Carcinomas | 188Re-SSS Lipiodol | Center Eugene Marquis |
17 January 2022/15 May 2024 Recruiting | Rhenium-Skin Cancer Therapy (SCT) for the Treatment of Non-Melanoma Skin Cancer. NCT05135052 | Efficacy of Personalized Irradiation with 188Rhenium-Skin Cancer Therapy (SCT) for the treatment of non-melanoma skin cancer. | Phase IV | Non-melanoma Skin Cancer. | 188Re-resin (Rhenium-SCT®) | OncoBeta International GmbH (OncoBeta Therapeutics) |
24 August 2020/30 September 2022 Recruiting | HER2 Expression Detection and Radionuclide Therapy in Breast Cancer Using 99mTc/188Re Labeled Single Domain Antibody NCT04674722 | To evaluate the safety, dosimetry, and efficacy of 99mTc/188Re labeled anti-HER2-single domain antibody (Product Code Name: 99mTc-NM-02 and 188Re-NM-02) SPECT/CT imaging of HER2 expression and radionuclide therapy in Breast Cancer. | Phase I | Breast Cancer Radiotoxicity | 99mTc or 188Re labeled anti-HER2 sdAb. | Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine |
16 May 2018/16 May 2024 Active, not recruiting | Rhenium-188-HEDP vs. Radium-223-chloride in Patients With Advanced Prostate Cancer Refractory to Hormonal Therapy. NCT03458559 | To investigate if treatment with 188Re-HEDP results in an improvement in overall survival compared to treatment with 223Ra-chloride. | Phase III | Prostate Cancer Metastatic to Bone. | 188Re-HEDP vs. 223RaChloride | Amsterdam UMC, location VUmc |
June 2017/June 2019 Withdrawn | Rhenium 188-P2045 in Small Cell Lung Cancer and Other Advanced Neuroendocrine Carcinomas. NCT02030184 | 188Re-P2045 in small lung cancer and other advanced NE carcinomas. | Phase I; Phase II | Small Cell Lung Cancer (SCLC); Neuroendocrine (NE) Tumors; Large Cell Neuroendocrine (NE) Tumors. | 188Re-P2045 | University of Maryland, Baltimore |
January 2004/April 2020 Unknown status | 188Re-P2045 in Patients With Lung Cancer Who Have Received or Refused to Receive Prior Chemotherapy. NCT00100256 | To determine the maximum dose that is safely tolerated for the experimental drug 188Re-P2045. | Phase I; Phase II | Lung Neoplasms Carcinoma; Non-Small-Cell Lung Carcinoma; Small Cell Neoplasm Recurrence. | 188Re-P2045 | Andarix Pharmaceuticals |
13 March 2017/31 October 2017 Unknown status | Treatment of Non-responding to Conventional Therapy Inoperable Liver Cancers by in Situ Introduction of ImDendrim. NCT03255343 | To evaluate the efficacy and safety of treatment of non-responding to conventional therapy inoperable liver cancers by in situ introduction of ImDendrim. | NA | Liver tumor non operable | [188Re]Complex Coupled to an Imidazolic Ligand and Associated With a Dendrime (Device) | French Association for the Advancement Medical Research |
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Uccelli, L.; Martini, P.; Urso, L.; Ghirardi, T.; Marvelli, L.; Cittanti, C.; Carnevale, A.; Giganti, M.; Bartolomei, M.; Boschi, A. Rhenium Radioisotopes for Medicine, a Focus on Production and Applications. Molecules 2022, 27, 5283. https://doi.org/10.3390/molecules27165283
Uccelli L, Martini P, Urso L, Ghirardi T, Marvelli L, Cittanti C, Carnevale A, Giganti M, Bartolomei M, Boschi A. Rhenium Radioisotopes for Medicine, a Focus on Production and Applications. Molecules. 2022; 27(16):5283. https://doi.org/10.3390/molecules27165283
Chicago/Turabian StyleUccelli, Licia, Petra Martini, Luca Urso, Teresa Ghirardi, Lorenza Marvelli, Corrado Cittanti, Aldo Carnevale, Melchiore Giganti, Mirco Bartolomei, and Alessandra Boschi. 2022. "Rhenium Radioisotopes for Medicine, a Focus on Production and Applications" Molecules 27, no. 16: 5283. https://doi.org/10.3390/molecules27165283