Dry-distillation of astatine-211 from irradiated bismuth targets: a time-saving procedure with high recovery yields

Lindegren, Sture; Bäck, Tom; Jensen, Holger

doi:10.1016/s0969-8043(01)00044-6

Cited by 126 publications

(80 citation statements)

References 8 publications

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“…Astatine-211 is generally produced by the bombardment of natural bismuth metal targets utilizing the 209 Bi(α, 2n) 211 At reaction. With the availability of internal target systems [12] and efficient dry distillation techniques [13], clinically relevant levels of 211 At can be readily obtained by utilizing incident α beams of 28-29 MeV. Unfortunately, however, there are only a few cyclotrons in the United States currently equipped with beams of this type, with the result that during the past 5 years, 211 At production has been limited to only three cyclotron facilities, those at University of Washington, the National Institutes of Health, and Duke University.…”

Section: Astatine-211 Labeled Mabs: Promise and Problemsmentioning

confidence: 99%

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

Zalutsky

Reardon

Pozzi

et al. 2007

Nuclear Medicine and Biology

114

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An attractive feature of targeted radionuclide therapy is the ability to select radionuclides and targeting vehicles with characteristics that are best suited for a particular clinical application. One combination that has been receiving increasing attention is the use of monoclonal antibodies specifically reactive to receptors and antigens that are expressed on tumor cells to selectively deliver the α-particle emitting radiohalogen 211 At to malignant cell populations. Promising results have been obtained in preclinical models with multiple 211 At-labeled mAbs; however, translation of concept to the clinic has been slow. Impediments to this process include limited radionuclide availability, the need for suitable radiochemistry methods operant at high activity levels, and the lack of data concerning toxicity of α-particle emitters in humans. Nonetheless, two clinical trials have been initiated to date with 211 At-labeled monoclonal antibodies and others are planned for the near future.

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Section: Astatine-211 Labeled Mabs: Promise and Problemsmentioning

confidence: 99%

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

Zalutsky

Reardon

Pozzi

et al. 2007

Nuclear Medicine and Biology

114

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“…The dry distillation system for isolation of the 211 At from the bismuth cyclotron target was a variation of a system described previously (19,20). The current distillation device uses a polyetheretherketone (PEEK) capillary loop (1.6-mm [ 1 / 16 -in] tubing, 1-mm inner diameter · 152-cm [5-ft] length) obtained from Upchurch Scientific instead of the glass vials that were used in the past (12) for trapping the 211 At activity.…”

Section: Production Of 211 At and Radiation Dose Calculationsmentioning

confidence: 99%

Radiopharmaceutical Chemistry of Targeted Radiotherapeutics, Part 3: -Particle-Induced Radiolytic Effects on the Chemical Behavior of 211At

Pozzi

Zalutsky²

2007

Journal of Nuclear Medicine

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Two characteristics of a-particles that enhance their potential for targeted radiotherapy are their high energy and approximately cellular range. Unfortunately, these properties also can have negative consequences, confounding the production of clinically relevant levels of radiopharmaceutical because of radiolytic effects. The purpose of this study was to evaluate the effect of radiation dose on the astatine species present before initiation of a labeling reaction and the potential role of these molecules in the efficiency of N-succinimidyl 3-211 At-astatobenzoate (SAB) synthesis. The ranges of radiation dose evaluated were selected to reflect those that might be encountered in SAB synthesis for the preparation of clinical doses of 211 At-labeled radiopharmaceuticals. Methods: The distribution of astatine species present in methanol, and the yields for the synthesis of SAB from N-succinimidyl 3-(tri-n-butylstannyl)benzoate as a function of radiation dose, were determined by high-performance liquid chromatography. Radiation doses in the range of 500-12,000 Gy were evaluated using different 211 At time-activity combinations, and the effect of acetic acid, a normal component of astatodestannylation reactions, also was studied. Finally, the effect of the reducing agent sodium sulfite also was evaluated to characterize the nature of the species produced by radiolysis. Results: At radiation doses below 1,000 Gy, high-performance liquid chromatography analysis indicated that more than 90% of the 211 At was present in methanol as a single species, At(1), whereas at higher doses, a second peak, At(2), emerged. At(1) decreased and At(2) increased in a radiation dose-dependent fashion, with At(2) becoming the predominant species at about 3,000 Gy. At(2) was identified as a reduced form of astatine, presumably astatide, which could not be efficiently oxidized to a species suitable for electrophilic astatination. In methanol/acetic acid, more than 95% of the astatine was present as At (2) even at doses below 1,400 Gy. Conclusion: The emergence of a reduced form of astatine, At(2), at higher radiation doses is consistent with the decline in SAB yields observed under these conditions. Alteration of the chemical form of the astatine by radiolysis could account for the declining yields noted in the preparation of clinical-level 211 At-labeled radiopharmaceuticals and when the labeling chemistry is initiated hours after 211 At production.

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“…The dry distillation of 211 At was conducted in a charcoal filtered glove box (Innovative Technologies, radioisotope glove box). The distilled 211 At was trapped in a cooled (−78°C) vial or peek tubing (1 mm ID × 35 cm length) (33) and was rinsed from the vial with CHCl 3 or 0.05 N NaOH for use in the labeling experiments.…”

Section: Radioactivitymentioning

confidence: 99%

Streptavidin in Antibody Pretargeting. 5. Chemical Modification of Recombinant Streptavidin for Labeling with the α-Particle-Emitting Radionuclides ²¹³Bi and ²¹¹At

et al. 2007

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We are investigating the use of recombinant streptavidin (rSAv) as a carrier molecule for the shortlived α-particle emitting radionuclides 213 Bi (t 1/2 = 45.6 min) and 211 At (t 1/2 = 7.21 h) in cancer therapy. To utilize rSAv as a carrier, it must be modified in a manner that permits rapid chelation or bonding with these short-lived radionuclides, and also modified in a manner that diminishes its natural propensity for localization in kidney. Modification for labeling with 213 Bi was accomplished by conjugation of rSAv with the DTPA derivative p-isothiocyanato-benzyl-CHX-A″ (CHX-A″), 3a. Modification for direct labeling with 211 At was accomplished by conjugation of rSAv with an isothiocyanatophenyl derivative of a nido-carborane (nCB), 3b, or an isothiocyanatophenyldPEG ™ /decaborate(2-) derivative, 3c. After conjugation of the chelating or bonding moiety, rSAv was further modified by reaction with an excess (50-100 equivalents) of succinic anhydride. Succinylation of the lysine amines has previously been shown to greatly diminish kidney localization. rSAv modified by conjugation with 3a and succinylated radiolabeled rapidly with 213 Bi (< 5 min), providing a 72% isolated yield. 211 At labeling of modified rSAv was accomplished in aqueous solution using chloramine-T as the oxidant. Astatination of rSAv conjugated with 3b and succinylated occurred very rapidly (<1 min), providing a 50% isolated radiochemical yield. Astatination of rSAv conjugated with 3c and succinylated was also very rapid (<1 min) providing 66-71% isolated radiochemical yields. Astatination of succinylated rSAv, 2a, which did not have conjugated borane cage moieties, resulted in much lower radiolabeling yield (18%). The 213 Bi-or 211 At-labeled modified rSAv preparations were mixed with the corresponding 125 I-labeled rSAv, and dual-label in vivo distributions were obtained in athymic mice. The in vivo data show that 213 Bi-labeled succinylated rSAv [ 213 Bi]6a has tissue concentrations similar to 125 I-labeled modified rSAv [ 125 I] 6b, suggesting that 213 Bi is quite stable towards release from the chelate in vivo. In vivo data also indicate that the 211 At-labeled rSAv conjugated with 3b or 3c and succinylated are stable to in vivo deastatination, whereas succinylated rSAv lacking a boron cage moiety is subject to some deastatination. The modified rSAv conjugated with nido-carborane derivative 3b has a higher retention in many tissues than rSAv without the carborane conjugated. Interestingly, the rSAv conjugated with 3c, which also contains a m-dPEG 12 ™ moiety, has significantly decreased concentrations in blood and other tissues when compared with direct labeled rSAv, suggesting that it may be a good candidate for further study. In conclusion, rSAv that has been modified with CHX-A″ and succinylated (i.e. 5a) may be useful as a carrier of 213 Bi. The encouraging results obtained with the PEGylated decaborate(2-) derivative 3c and succinylated (i.e. 5c) suggests that its further study as a carrier of 211 At in pretargeting prot...

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Dry-distillation of astatine-211 from irradiated bismuth targets: a time-saving procedure with high recovery yields

Cited by 126 publications

References 8 publications

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

Radiopharmaceutical Chemistry of Targeted Radiotherapeutics, Part 3: -Particle-Induced Radiolytic Effects on the Chemical Behavior of 211At

Streptavidin in Antibody Pretargeting. 5. Chemical Modification of Recombinant Streptavidin for Labeling with the α-Particle-Emitting Radionuclides ²¹³Bi and ²¹¹At

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Dry-distillation of astatine-211 from irradiated bismuth targets: a time-saving procedure with high recovery yields

Cited by 126 publications

References 8 publications

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

Radiopharmaceutical Chemistry of Targeted Radiotherapeutics, Part 3: -Particle-Induced Radiolytic Effects on the Chemical Behavior of 211At

Streptavidin in Antibody Pretargeting. 5. Chemical Modification of Recombinant Streptavidin for Labeling with the α-Particle-Emitting Radionuclides 213Bi and 211At

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Product

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Streptavidin in Antibody Pretargeting. 5. Chemical Modification of Recombinant Streptavidin for Labeling with the α-Particle-Emitting Radionuclides ²¹³Bi and ²¹¹At