An overview of radioisotope separation technologies for development of 188W/188Re radionuclide generators providing 188Re to meet future research and clinical demands

Dash, Ashutosh; Knapp, F. F.

doi:10.1039/c5ra03890a

Cited by 16 publications

(8 citation statements)

References 85 publications

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“…As demonstrated in our previous work [19, 20], 188 Re 155 keV γ -emissions allow us to perform quantitative 188 Re SPECT imaging which can be used for accurate image-based dosimetry. In addition, the availability of 188 Re through the 188 W/ 188 Re generator [21–23] makes the treatment less costly and more practical than 90 Y, because 188 Re can be produced on site in the nuclear medicine department.…”

Section: Introductionmentioning

confidence: 99%

Biodistribution, pharmacokinetics, and organ-level dosimetry for 188Re-AHDD-Lipiodol radioembolization based on quantitative post-treatment SPECT/CT scans

et al. 2018

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BackgroundRhenium-188-labelled-Lipiodol radioembolization is a safe and cost-effective treatment for primary liver cancer. In order to determine correlations between treatment doses and patient response to therapy, accurate patient-specific dosimetry is required. Up to date, the reported dosimetry of 188Re-Lipiodol has been based on whole-body (WB) planar imaging only, which has limited quantitative accuracy. The aim of the present study is to determine the in vivo pharmacokinetics, bio-distribution, and organ-level dosimetry of 188Re-AHDD-Lipiodol radioembolization using a combination of post-treatment planar and quantitative SPECT/CT images. Furthermore, based on the analysis of the pharmacokinetic data, a practical and relatively simple imaging and dosimetry method that could be implemented in clinics for 188Re-AHDD-Lipiodol radioembolization is proposed.Thirteen patients with histologically proven hepatocellular carcinoma underwent 188Re-AHDD-Lipiodol radioembolization. A series of 2–3 WB planar images and one SPECT/CT scan were acquired over 48 h after the treatment. The time-integrated activity coefficients (TIACs, also known as residence-times) and absorbed doses of tumors and organs at risk (OARs) were determined using a hybrid WB/SPECT imaging method.ResultsWhole-body imaging showed that 188Re-AHDD-Lipiodol accumulated mostly in the tumor and liver tissue but a non-negligible amount of the pharmaceutical was also observed in the stomach, lungs, salivary glands, spleen, kidneys, and urinary bladder. On average, the measured effective half-life of 188Re-AHDD-Lipiodol was 12.5 ± 1.9 h in tumor. The effective half-life in the liver and lungs (the two organs at risk) was 12.6 ± 1.7 h and 12.0 ± 1.9 h, respectively. The presence of 188Re in other organs was probably due to the chemical separation and subsequent release of the free radionuclide from Lipiodol.The average doses per injected activity in the tumor, liver, and lungs were 23.5 ± 40.8 mGy/MBq, 2.12 ± 1.78 mGy/MBq, and 0.11 ± 0.05 mGy/MBq, respectively. The proposed imaging and dosimetry method, consisting of a single SPECT/CT for activity determination followed by 188Re-AHDD-Lipiodol clearance with the liver effective half-life of 12.6 h, resulted in TIACs estimates (and hence, doses) mostly within ± 20% from the reference TIACs (estimated using three WB images and one SPECT/CT).ConclusionsThe large inter-patient variability of the absorbed doses in tumors and normal tissue in 188Re-HDD-Lipiodol radioembolization patients emphasizes the importance of patient-specific dosimetry calculations based on quantitative post-treatment SPECT/CT imaging.Electronic supplementary materialThe online version of this article (10.1186/s40658-018-0227-6) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Biodistribution, pharmacokinetics, and organ-level dosimetry for 188Re-AHDD-Lipiodol radioembolization based on quantitative post-treatment SPECT/CT scans

et al. 2018

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“…These results indicate that t viable for preparing the homologous Tc-99m. They are also informative a studies for preparing the metal complexes with the β-emitting radionuclid 188, which are useful for therapeutic purposes [29,37,38]. Complexes 2 Re and 3 Re were characterized by common spectroscopic and spectrometric methods ( 1 H, 13 C, 31 P NMR, IR and HRMS can be found as Supplementary Materials).…”

Section: Rhenium Complexesmentioning

confidence: 99%

New Bioconjugated Technetium and Rhenium Folates Synthesized by Transmetallation Reaction with Zinc Derivatives

et al. 2021

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The zinc dithiocarbamates functionalized with folic acid 2Zn and 3Zn were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate (1Zn). Zinc complexes 2Zn and 3Zn show very low solubilities in water, making them useful for preparing Tc-99m radiopharmaceuticals with a potentially high molar activity. Thus, the transmetallation reaction in water medium between the zinc complexes 2Zn or 3Zn and the cation fac-[99mTc(H2O)3(CO)3]+, in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes fac-[99mTc(CO)3(SS)(P)] bioconjugated to folic acid (2Tc and 3Tc). In spite of the low solubility of 2Zn and 3Zn in water, the reaction yield is higher than 95%, and the excess zinc reagent is easily removed by centrifugation. The Tc-99m complexes were characterized by comparing their HPLC with those of the homologous rhenium complexes (2Re and 3Re) previously synthesized and characterized by standard methods. Preliminary in vivo studies with 2Tc and 3Tc indicate low specific binding to folate receptors. In summary, Tc-99m folates 2Tc and 3Tc were prepared in high yields, using a one-pot transmetallation reaction with low soluble zinc dithiocarbamates (>1 ppm), at moderate temperature, without needing a subsequent purification step.

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“…Rhenium-188 (T ½ = 16.9 h, E max = 2.12 MeV, 155 keV γ-ray) is an established therapeutic radioisotope that can be obtained in a no-carrier-added (NCA) form via 188 W/ 188 Re generator for preparation of a wide variety of radiopharmaceuticals [10]. The parent 188 W can be produced with adequate specific activity by double neutron capture i.e.…”

Section: Introductionmentioning

confidence: 99%

“…The parent 188 W can be produced with adequate specific activity by double neutron capture i.e. 186 W (n,γ) 187 W (n,γ) 188 W reaction on enriched 186 W target in high flux research reactors (> 10 15 n•cm −2 •s −1 ) [10]. There are only very few operational high flux research reactors in the world.…”

Section: Introductionmentioning

confidence: 99%

“…Utilization of LSA 188 W produced in these research reactors mandates the need for high capacity advanced sorbent materials for preparation of clinically useful 188 W/ 188 Re generators. In the past, many high capacity sorbent materials such as polymeric zirconium compound, polymeric titantium oxychloride, synthetic alumina, polymer embedded nanocrystalline titania, nanocrystalline zirconia and nanocrystalline alumina, etc., have been reported for preparation of chromatographic 188 W/ 188 Re generators [10,[12][13][14][15][16][17][18][19]. Despite their high sorption capacity, most of these generators used high specific activity 188 W produced in high flux research reactors.…”

Section: Introductionmentioning

confidence: 99%

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Mechanochemically synthesized mesoporous alumina: a smart new-generation sorbent for preparation of chromatographic 188W/188Re generator

et al. 2021

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In an effort towards affordable availability of chromatographic 188W/188Re generators for widespread clinical use, we report the mechanochemical synthesis of mesoporous alumina as an advanced sorbent material for preparation of the generator. The synthesized material exhibits remarkably high sorption capacity (550 ± 12 mg W/g), which is adequate for preparation of clinical-scale generators using low specific activity (LSA) 188W produced in medium flux research reactors. Sorption of 188W in mesoporous alumina follows Freundlich adsorption isotherm and pseudo second order kinetics, indicating that the process is chemisorption. A clinical-scale (~ 14.0 GBq) 188W/188Re generator was developed and its performance was evaluated over a period of 6 months. Rhenium-188 could be consistently obtained from the generator with high yield (> 80%) and it met all the requirements for clinical use. The present strategy is expected to increase the scope of separation chemistry for availing clinical-grade 188Re for the benefit of millions of cancer patients world over. Graphic abstract

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An overview of radioisotope separation technologies for development of ¹⁸⁸W/¹⁸⁸Re radionuclide generators providing ¹⁸⁸Re to meet future research and clinical demands

Abstract: Separation technologies for 188W/188Re radionuclide generators.

Cited by 16 publications

References 85 publications

Biodistribution, pharmacokinetics, and organ-level dosimetry for 188Re-AHDD-Lipiodol radioembolization based on quantitative post-treatment SPECT/CT scans

Biodistribution, pharmacokinetics, and organ-level dosimetry for 188Re-AHDD-Lipiodol radioembolization based on quantitative post-treatment SPECT/CT scans

New Bioconjugated Technetium and Rhenium Folates Synthesized by Transmetallation Reaction with Zinc Derivatives

Mechanochemically synthesized mesoporous alumina: a smart new-generation sorbent for preparation of chromatographic 188W/188Re generator

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