Spectrophotometric method for the determination of a bifunctional DTPA ligand in DTPA-monoclonal antibody conjugates

Cg, Pippin; Ta, Parker; Tj, McMurry; Mw, Brechbiel

doi:10.1021/bc00016a014

Cited by 139 publications

(117 citation statements)

References 13 publications

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“…5 a-c, which is published as supporting information on the PNAS web site, shows the percent initial dose per g in CN-infected A͞JCr mice in comparison with the healthy controls. At all three time intervals (24,48, and 72 h), the uptake of radioactivity in the liver and spleen of infected mice given 188 Re-18B7 was higher (P Ͻ 0.05) than in control groups, which is the consequence of the deposition of antibody-antigen complex (10). In contrast, the activity in the blood of noninfected mice was significantly higher than in infected mice (P Ͻ 0.05), which also resulted in higher uptake of 188 Re-18B7 mAb in the brain of healthy mice.…”

Section: Biodistribution Of Radiolabeled 18b7 Mab In Locally Infectedmentioning

confidence: 99%

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

Dadachova

Nakouzi

Bryan³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

115

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There is an urgent need for new antimicrobial therapies to combat drug resistance, new pathogens, and the relative inefficacy of current therapy in compromised hosts. Ionizing radiation can kill microorganisms quickly and efficiently, but this modality has not been exploited as a therapeutic antimicrobial strategy. We have developed methods to target ionizing radiation to a fungal cell by labeling a specific mAb with the therapeutic radioisotopes Rhenium-188 and Bismuth-213. Radiolabeled antibody killed cells of human pathogenic fungus Cryptococcus neoformans in vitro, thus converting an antibody with no inherent antifungal activity into a microbicidal molecule. Administration of radiolabeled antibody to mice with C. neoformans infection delivered 213 Bi and 188 Re to the sites of infection, reduced their organ fungal burden, and significantly prolonged their survival without apparent toxicity. This study establishes the principle that targeted radiation can be used for the therapy of an infectious disease, and suggests that it may have wide applicability as an antimicrobial strategy.

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Section: Biodistribution Of Radiolabeled 18b7 Mab In Locally Infectedmentioning

confidence: 99%

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

Dadachova

Nakouzi

Bryan³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

115

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“…The final concentration of the CHX-AЉ-DTPA-anti-IL-2 Ab was quantitated by the Lowry method (39). The number of CHX-AЉ molecules linked to the Ab was determined using a spectrophotometric assay based on the titration of Y(III)-Arsenazo(III) complex (40).…”

Section: Ab Conjugation and Radiolabelingmentioning

confidence: 99%

IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8+ T Cell Responses and Increases the Ratio of Effector/Memory CD8+ T Cells to Regulatory T Cells

Mostböck

Lutsiak

Milenic

et al. 2008

The Journal of Immunology

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IL-2 is well described as a cytokine with two markedly distinct functionalities: as a necessary signal during CD4+ and CD8+ T cell activation/expansion and as an essential cytokine for the maintenance of CD4+CD25+FoxP3+ T cells (regulatory T (TREG) cells) during homeostasis. In this study we demonstrate for the first time that, compared with the use of IL-2 alone, a complex of IL-2 and anti-IL-2 Ab (IL-2 complex) enhances the effectiveness of a viral vaccine in a mouse model with known Ag specificity. IL-2 complex led to an increase in the number of Ag-specific effector/memory CD8+ T cells, cytokine production, and CTL lysis following Ag-specific restimulation in a vaccination setting. Our results further demonstrate that this effect is temporary and declines over the course of a few days after the IL-2 complex treatment cycle. Moreover, in contrast to the use of IL-2 alone, IL-2 complex greatly increased the ratio of effector/memory CD8+ T cells to TREG cells. This phenomenon can thus potentially be used in the enhancement of immune responses to vaccination.

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“…The number of CHX-A″ chelates per rSAv molecule in 5a was assessed using the yttrium-arsenazo III complex spectrophotometric assay (37). The modified rSAv was stored at 4°C until used.…”

Section: Preparation Of Succinylated Rsav-chx-a″ 5amentioning

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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Spectrophotometric method for the determination of a bifunctional DTPA ligand in DTPA-monoclonal antibody conjugates

Cited by 139 publications

References 13 publications

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8+ T Cell Responses and Increases the Ratio of Effector/Memory CD8+ T Cells to Regulatory T Cells

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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Spectrophotometric method for the determination of a bifunctional DTPA ligand in DTPA-monoclonal antibody conjugates

Cited by 139 publications

References 13 publications

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8+ T Cell Responses and Increases the Ratio of Effector/Memory CD8+ T Cells to Regulatory T Cells

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