Pharmacokinetics of the disialoganglioside, GD2, a circulating tumor biomarker for neuroblastoma, in nonhuman primates

Authors

DOI:

https://doi.org/10.33393/jcb.2021.2329

Keywords:

biomarker, ganglioside, Neuroblastoma, Pharmacokinetics

Abstract

Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer, neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology.

Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology.

Methods: We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of the C18 lipoform of GD2 in two nonhuman primates with indwelling subcutaneous CSF lateral ventricular reservoir systems. GD2 was quantified with a validated high-performance liquid chromatography (HPLC)/tandem mass spectrometry assay. GD2 was administered as a short intravenous infusion and frequent plasma and CSF samples were drawn over 72 hours.

Results: GD2 plasma concentration declined monoexponentially with a half-life of 16 hours. Clearance was 0.0136 and 0.0131 L/h and volume of distribution (Vd) was 0.035 and 0.038 L/kg in the two animals. Vd was equivalent to plasma volume. Greater than 98% of GD2 in plasma is in a bound form consistent with its known association with lipoproteins and accounting for its limited volume of distribution. GD2 did not cross over from plasma into the CSF.

Conclusions: The pharmacokinetic profile of GD2 is favorable for a circulating tumor biomarker. This study demonstrates the value of characterizing the clinical pharmacology of circulating biomarkers to better understand their clinical behavior.

Downloads

Download data is not yet available.

References

Balis FM, Busch CM, Desai AV, et al. The ganglioside GD2 as a circulating tumor biomarker for neuroblastoma. Pediatr Blood Cancer. 2020;67(1):e28031. https://doi.org/10.1002/pbc.28031PMID:31612589 DOI: https://doi.org/10.1002/pbc.28031

Lester McCully CM, Bacher J, MacAllister RP, et al. Development of a cerebrospinal fluid lateral reservoir model in rhesus monkeys (Macaca mulatta). Comp Med. 2015;65(1):77-82. PMID:25730761

Guide for care and use of laboratory animals. 8th ed. Washington, DC: The National Academies Press 2011. http://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-of-laboratory-animals.pdf

Busch CM, Desai AV, Moorthy GS, Fox E, Balis FM. A validated HPLC-MS/MS method for estimating the concentration of the ganglioside, GD2, in human plasma or serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1102-1103:60-65. https://doi.org/10.1016/j.jchromb.2018.10.010 PMID:30368044 DOI: https://doi.org/10.1016/j.jchromb.2018.10.010

Hobbs TR, Blue SW, Park BS, Greisel JJ, Conn PM, Pau FK. Measurement of blood volume in adult rhesus macaques (Macaca mulatta). J Am Assoc Lab Anim Sci. 2015;54(6):687-693. PMID:26632777

Ladisch S, Wu ZL, Feig S, et al. Shedding of GD2 ganglioside by human neuroblastoma. Int J Cancer. 1987;39(1):73-76. https://doi.org/10.1002/ijc.2910390113 PMID:3539825 DOI: https://doi.org/10.1002/ijc.2910390113

Baratz E, McCully C, Shih J, Warren K. Comparison of pharmacokinetic parameters between non-human primates and human patients. Neuro-oncol. 2018;20(suppl 2):i157. https://doi.org/10.1093/neuonc/noy059.582 DOI: https://doi.org/10.1093/neuonc/noy059.582

Valentino LA, Ladisch S. Localization of shed human tumor gangliosides: association with serum lipoproteins. Cancer Res. 1992;52(4):810-814. PMID:1737341

Published

2021-12-03

How to Cite

Balis, F. M., Lester McCully, C., Busch, C. M., Fox, E., & Warren, K. E. (2021). Pharmacokinetics of the disialoganglioside, GD2, a circulating tumor biomarker for neuroblastoma, in nonhuman primates. Journal of Circulating Biomarkers, 10(1), 26–29. https://doi.org/10.33393/jcb.2021.2329

Issue

Section

Original research article
Received 2021-08-06
Accepted 2021-11-22
Published 2021-12-03

Metrics