Pharmacokinetics of the disialoganglioside, G(D2), a circulating tumor biomarker for neuroblastoma, in nonhuman primates

BACKGROUND: The ganglioside G(D2) 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 C(18) lipoform of G(D2) in two nonhuman primates with indwelling subcutaneous CSF lateral ventricular reservoir systems. G(D2) was quantified with a validated high-performance liquid chromatography (HPLC)/tandem mass spectrometry assay. G(D2) was administered as a short intravenous infusion and frequent plasma and CSF samples were drawn over 72 hours. RESULTS: G(D2) plasma concentration declined monoexponentially with a half-life of 16 hours. Clearance was 0.0136 and 0.0131 L/h and volume of distribution (V(d)) was 0.035 and 0.038 L/kg in the two animals. V(d) was equivalent to plasma volume. Greater than 98% of G(D2) in plasma is in a bound form consistent with its known association with lipoproteins and accounting for its limited volume of distribution. G(D2) did not cross over from plasma into the CSF. CONCLUSIONS: The pharmacokinetic profile of G(D2) 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.