A systematic study on the utility of CHX-A’’-DTPA-NCS and NOTA-NCS as bifunctional chelators for 177 Lu radiopharmaceuticals

Pandey, Usha; Gamre, Naresh; Lohar, Sharad P.; Dash, Ashutosh

doi:10.1016/j.apradiso.2017.04.028

Cited by 17 publications

(10 citation statements)

References 27 publications

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“…For example, when the 111 In radiolabel is used for labeling antibodies the pharmacokinetics in mice could be followed for up to 7 days, as the physical half-life is 2.8 days. If much later time points are desirable, longer lived radionuclides such 177 Lutetium, which also forms stable complexes with CHXA” bifunctional chelating agent [6] and has a 6.7-day physical half-life, could be used in place of 111 In. Collection of data from at least 4–5 time points would enable the modeling of blood clearance of the antibodies using biphasic models, as well as allowing radiation dosimetry calculations if an antibody-based imaging or radioimmunotherapeutic agent is being developed.…”

Section: Discussionmentioning

confidence: 99%

Biodistribution of a Radiolabeled Antibody in Mice as an Approach to Evaluating Antibody Pharmacokinetics

et al. 2018

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(1) Background: Monoclonal antibodies are used in the treatment of multiple conditions including cancer, autoimmune disorders, and infectious diseases. One of the initial steps in the selection of an antibody candidate for further pre-clinical development is determining its pharmacokinetics in small animal models. The use of mass spectrometry and other techniques to determine the fate of these antibodies is laborious and expensive. Here we describe a straightforward and highly reproducible methodology for utilizing radiolabeled antibodies for pharmacokinetics studies. (2) Methods: Commercially available bifunctional linker CHXA” and 111Indium radionuclide were used. A melanin-specific chimeric antibody A1 and an isotype matching irrelevant control A2 were conjugated with the CHXA”, and then radiolabeled with 111In. The biodistribution was performed at 4 and 24 h time points in melanoma tumor-bearing and healthy C57BL/6 female mice. (3) The biodistribution of the melanin-binding antibody showed the significant uptake in the tumor, which increased with time, and very low uptake in healthy melanin-containing tissues such as the retina of the eye and melanized skin. This biodistribution pattern in healthy tissues was very close to that of the isotype matching control antibody. (4) Conclusions: The biodistribution experiment allows us to assess the pharmacokinetics of both antibodies side by side and to make a conclusion regarding the suitability of specific antibodies for further development.

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Section: Discussionmentioning

confidence: 99%

Biodistribution of a Radiolabeled Antibody in Mice as an Approach to Evaluating Antibody Pharmacokinetics

et al. 2018

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“…Placental transfer studies were performed by inviCRO (Boston, MA). For these studies, a poly IgG fraction was isolated from rats previously exposed to the GBS6 CGS conjugate vaccine and conjugated to CHX‐A‐DTPA, a chelator for the radiolabel (Pandey, Gamre, Lohar, & Dash, 2017). To investigate the placental transfer of poly IgG generated from GBS6 vaccination, female 12‐week old rats ( n = 10) were bolus injected intravenously on GD 19 with approximately 400 μl of 111 In‐DTPA‐pAg at a target radioactivity of 400–500 μCi (3 mg/kg) at hour intervals so they could undergo imaging at the same time.…”

Section: Methodsmentioning

confidence: 99%

Maternal immunization with Group B Streptococcus six‐valent polysaccharide conjugate vaccine supported by lack of toxicity in rat and rabbit fertility and developmental toxicity studies

Catlin

Cappon

Engel

et al. 2021

Birth Defects Research

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A maternal Group B Streptococcus (GBS) six‐valent polysaccharide conjugate vaccine (GBS6) is being developed to protect neonates and infants up to 3 months of age through passive transfer of antibodies from the mother to the infant. Fertility and developmental toxicity studies were conducted in female Sprague Dawley rats and New Zealand White rabbits with GBS6 (20 μg capsular polysaccharide/serotype formulated with or without AlPO4, the highest clinical dose). Females were administered the full human dose of the GBS6 formulation intramuscularly twice prior to mating and twice during gestation, to ensure that high antibody levels were maintained throughout gestation and lactation. Approximately, half of the rats and rabbits were evaluated at the end of gestation, and the remainder were evaluated at the end of lactation. Maternal blood for GBS6 serology, to measure antibody titers to the GBS6 antigens, was collected prior to the first dose, prior to mating, and at each necropsy. Blood for serology was also collected from offspring at the end of gestation and lactation. In both species, there was no evidence of vaccine‐related effects on fertility, embryo‐fetal development, or postnatal development of the offspring, supporting regulatory guidance that single‐species evaluation would have been sufficient. Functional serum antibodies to all six serotypes in the vaccine were confirmed in maternal animals and functional serum antibodies to one or more of the six serotypes was also confirmed in some rat offspring and most of the rabbit offspring. The results of these studies supported the safety of GBS6 vaccine administration to pregnant women.

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“…CHX-A”-DTPA has been reported to have been used for several radionuclides such as 111 In, 90 Y, 177 Lu, and 212/213 Bi ( Table 4 ) [ 109 , 130 ]. Several studies have shown that CHX-A”-DTPA-based radiopharmaceuticals complexed with 111 In, 90 Y, 177 Lu, and 212/213 Bi have better stability than DTPA and 1B4M-DTPA [ 131 , 132 ]. Radiolabeling of CHX-A”-DTPA and radionuclides occur under room temperature conditions and pH of 5.0–5.5 in 10–30 min [ 109 ].…”

Section: Bifunctional Chelator Used In Radiopharmaceutical Agentsmentioning

confidence: 99%

The Chemical Scaffold of Theranostic Radiopharmaceuticals: Radionuclide, Bifunctional Chelator, and Pharmacokinetics Modifying Linker

et al. 2022

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Therapeutic radiopharmaceuticals have been researched extensively in the last decade as a result of the growing research interest in personalized medicine to improve diagnostic accuracy and intensify intensive therapy while limiting side effects. Radiometal-based drugs are of substantial interest because of their greater versatility for clinical translation compared to non-metal radionuclides. This paper comprehensively discusses various components commonly used as chemical scaffolds to build radiopharmaceutical agents, i.e., radionuclides, pharmacokinetic-modifying linkers, and chelators, whose characteristics are explained and can be used as a guide for the researcher.

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A systematic study on the utility of CHX-A’’-DTPA-NCS and NOTA-NCS as bifunctional chelators for 177 Lu radiopharmaceuticals

Cited by 17 publications

References 27 publications

Biodistribution of a Radiolabeled Antibody in Mice as an Approach to Evaluating Antibody Pharmacokinetics

Biodistribution of a Radiolabeled Antibody in Mice as an Approach to Evaluating Antibody Pharmacokinetics

Maternal immunization with Group B Streptococcus six‐valent polysaccharide conjugate vaccine supported by lack of toxicity in rat and rabbit fertility and developmental toxicity studies

The Chemical Scaffold of Theranostic Radiopharmaceuticals: Radionuclide, Bifunctional Chelator, and Pharmacokinetics Modifying Linker

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