Biodistribution and lymphatic tracking of the main neurotoxin of micrurus fulvius venom by molecular imaging

The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β -NTx). The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β -NTx of M. fulvius venom. β -NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA) and radiolabeled with the radionuclide Gallium-⁶⁷. Radiolabeling efficiency was 60%-78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD₅₀) and PLA₂ activity of bioconjugated β -NTx decreased 3 and 2.5 times, respectively, in comparison with native β -NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β -NTx-DTPA-⁶⁷Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with⁶⁷Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β -NTx-DTPA-⁶⁷Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β -NTx-DTPA-⁶⁷Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.