Applying quality by design principles to the small-scale preparation of the bone-targeting therapeutic radiopharmaceutical rhenium-188-HEDP

Lange, Rogier; Heine, Rob ter; Gronde, Toon van der; Selles, Suzanne; Klerk, John de; Bloemendal, Haiko J.; Hendrikse, Harry

doi:10.1016/j.ejps.2016.01.008

Cited by 14 publications

(6 citation statements)

References 27 publications

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“…The multiple-vial kit demonstrated very robust radiolabelling yields and radiochemical purities above 95% [ 29 , 53 ]. Although the amount of cold rhenium carrier is critical to obtain a radiopharmaceutical with the necessary radiochemical purity as well as the physiological bone uptake needed to elicit the therapeutic response [ 54 ], this result was achieved at the cost of a lower radionuclidic purity that, obviously, decreased the effective dose deposited on the bone lesions. Bisphosphonates labelled with 188 Re [ 55 ] for bone pain palliation have demonstrated impressive results in clinical studies.…”

Section: Matching the Nuclear And Biological Properties Of ...mentioning

confidence: 99%

“…Therapy with [ 188 Re]Re(HEDP) has demonstrated an improvement in overall survival and progression-free survival in patients with bone metastases and even a reduction in prostate-specific antigen (PSA) levels in metastatic castration-resistant prostate cancer patients. Therefore, 188 Re-based therapy might elicit an additional antitumor effect not restricted to pain palliation [ 30 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

Section: Matching the Nuclear And Biological Properties Of ...mentioning

confidence: 99%

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Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

2023

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The β− emitter, rhenium-188 (188Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (99mTc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention. This review aims to highlight what needs to be considered to design a successful radiopharmaceutical incorporating 118Re. Some of the most effective strategies for preparing therapeutic radiopharmaceuticals with 188Re are illustrated and rationalized using the concept of the inorganic functional group (core) and a simple ligand field theoretical model combined with a qualitative definition of frontiers orbitals. Of special interest are the Re(V) oxo and Re(V) nitrido functional groups. Suitable ligands for binding to these cores are discussed, successful clinical applications are summarized, and a prediction of viable future applications is presented. Rhenium-188 decays through the emission of a high energy beta particle (2.12 MeV max energy) and a half-life of 16.9 h. An ideal biological target would therefore be a high-capacity target site (transporters, potential gradients, tumour microenvironment) with less emphasis on saturable targets such as overexpressed receptors on smaller metastases.

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Section: Matching the Nuclear And Biological Properties Of ...mentioning

confidence: 99%

Section: Matching the Nuclear And Biological Properties Of ...mentioning

confidence: 99%

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

2023

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“…An important point in the preparation of 188 Re-HEDP is the necessity of decreasing the specific activity by adding “cold” rhenium ( aka carrier) in order to have good bone fixation. Several studies have investigated the influence of the reaction conditions and kit composition on final product's stability and in vivo behavior (110–118). All of them pointed out that the addition of carrier was crucial.…”

Section: Re-labeled Small Moleculesmentioning

confidence: 99%

“…All of them pointed out that the addition of carrier was crucial. A GMP grade kit for the preparation of 188 Re-HEDP has recently been described (119) and a standard procedure following the ICH Q8 guideline, and investigating the critical step parameters, has been reported by the same team (118).…”

Section: Re-labeled Small Moleculesmentioning

confidence: 99%

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives

et al. 2019

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Rhenium-188 ( 188 Re) is a high energy beta-emitting radioisotope with a short 16.9 h physical half-life, which has been shown to be a very attractive candidate for use in therapeutic nuclear medicine. The high beta emission has an average energy of 784 keV and a maximum energy of 2.12 MeV, sufficient to penetrate and destroy targeted abnormal tissues. In addition, the low-abundant gamma emission of 155 keV (15%) is efficient for imaging and for dosimetric calculations. These key characteristics identify 188 Re as an important therapeutic radioisotope for routine clinical use. Moreover, the highly reproducible on-demand availability of 188 Re from the 188 W/ 188 Re generator system is an important feature and permits installation in hospital-based or central radiopharmacies for cost-effective availability of no-carrier-added (NCA) 188 Re. Rhenium-188 and technetium-99 m exhibit similar chemical properties and represent a “theranostic pair.” Thus, preparation and targeting of 188 Re agents for therapy is similar to imaging agents prepared with 99m Tc, the most commonly used diagnostic radionuclide. Over the last three decades, radiopharmaceuticals based on 188 Re-labeled small molecules, including peptides, antibodies, Lipiodol and particulates have been reported. The successful application of these 188 Re-labeled therapeutic radiopharmaceuticals has been reported in multiple early phase clinical trials for the management of various primary tumors, bone metastasis, rheumatoid arthritis, and endocoronary interventions. This article reviews the use of 188 Re-radiopharmaceuticals which have been investigated in patients for cancer treatment, demonstrating that 188 Re represents a cost effective alternative for routine clinical use in comparison to more expensive and/or less readily available therapeutic radioisotopes.

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“…Although the earlier routine effective clinical use of 188 Re-HEDP spanned over several years in Germany (Bonn and Kassel) and elsewhere, use of this agent at these centers is evidently not currently in progress. However, recent renewed interest in the benefits of using 188 Re-HEDP for treatment of intractable skeletal pain form metastases are reflected in the efficacious reports of studies in progress at the Meander Medical Center in The Netherlands [32][33][34][35][36] and in Coimbatore, India [37]. At the Meander Center, in house routine GMP production of Re-HEDP is also being evaluated [37].…”

Section: Sm and 186mentioning

confidence: 99%

Important Clinical Applications of 188Rhenium for Radionuclide Therapy

Shinto¹

2017

Int. J. Nucl. Medi. Res.

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Although established clinical utility is of key importance in choosing agents for radionuclide therapy, other key factors include costs and GMP availability of sterile, pyrogen-free, regulatory approved radiopharmaceuticals. No-carrieradded (NCA) 188 Rhenium(188 Re, 16.9 hour half-life; 155 keV gamma emission) is available on demand as 188 Reperrhenate from saline elution of a 188 Tungsten/ 188 Rhenium(188 W/ 188 Re) generator. The availability and superb radionuclidic and chemical properties make 188 Re an excellent candidate for radionuclide therapy. This radioisotope is readily attached to a variety of targeting agents and also emits high energy beta particles (Emax 2.12 MeV) for therapy. Over the last 30 years the effectiveness of 188 Re for a variety of therapeutic applications has been established in multiple clinical studies. This overview provides a brief summary of clinical applications with 188 Re-labeled agents as an introduction to the detailed clinical discussions in the following papers. Although 188 Re-labeled radiopharmaceuticals for routine clinical use and accompanying reimbursement are not yet commercially available, several agents have been evaluated in clinical studies. In addition, a large number of 188 Re radiopharmaceutical agents have been developed and evaluated in pre-clinical studies over the last three decades. This review focuses on providing examples of 188 Re-labeled radiopharmaceutical agents which have entered late stage clinical use and have demonstrated good efficacy. These key applications include palliative treatment of skeletal metastases, intra-arterial therapy of liver cancer and post PTCA intravascular inhibition of arterial restenosis. Also, 188 Re radiopharmaceuticals had been developed and initially assessed for synovectomy and for marrow suppression. More recently, a unique device-based technology has entered clinical use for therapy of non-melanoma skin cancer using a 188 Re topical cream. Finally, 188 Re-antibodies are being developed for the potential therapy of infectious disease and this unique new therapeutic strategy is expected to enter clinical trials in the near future.

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Applying quality by design principles to the small-scale preparation of the bone-targeting therapeutic radiopharmaceutical rhenium-188-HEDP

Cited by 14 publications

References 27 publications

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives

Important Clinical Applications of 188Rhenium for Radionuclide Therapy

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