On the prevention of kidney uptake of radiolabeled DARPins

EJNMMI Research

Table 1 List of compounds that were administered to mice before injections of radiolabeled DARPins

Compound	Suggested mechanism of action in the kidney	Route of administration	Administration respective to the radiolabeled DARPin	Dose	LD₅₀
Lysine	Blocks megalin ligand-binding domains	i.v.	Co-injection	1200 mg/kg	4000 mg/kg (i.p., rat)
Gelofusine	Blocks megalin ligand-binding domains	i.v.	Co-injection	160 mg/kg	n/a
Sodium maleate	Inhibits ATP-mediated endocytosis	i.v.	5 min before	480 mg/kg	600 mg/kg (i.p., rat) 3380 mg/kg (oral, rat)
Mannitol	Diuretic, reduces contact time with scavenger receptors	i.v.	5 min before	480 mg/kg	7470 mg/kg (i.v., mouse)
Furosemide	Diuretic, reduces contact time with scavenger receptors	i.v.	5 min before	3 mg/kg	800 mg/kg (i.p., rat)
Fructose	Inhibits ATP-mediated endocytosis	i.p.	5 min before	10,800 mg/kg (60 mmol/kg)	15,000 mg/kg (83 mmol/kg)
Probenecid	Reduces renal excretion of drugs by inhibiting organic anion transporter	i.p.	1 h before	24 mg/kg	1000 mg/kg (i.p., mouse)
Colchicine	Inhibits recycling of megalin by disrupting microtubules	i.p.	5 h before	1.2 mg/kg	1.6 mg/kg (i.p., mouse)