MODAG-005

MODAG-005 is a blood-brain barrier-permeable PET probe precursor for α-synuclein ( α‑Syn ) aggregates, with a K i value of 0.4 nM and a K d value of 0.2 nM. MODAG-005 specifically binds to high-affinity sites within the tubular cavity of α-synuclein fibrils, and exhibits selectivity over tau protein fibrils and β-amyloid (A 1-42 ) fibrils. MODAG-005 is applicable to the research of multiple system atrophy and Parkinson's disease ^[1].

In Vivo, [11C]MODAG-005 (intravenous administration; single bolus injection) exhibits rapid brain uptake, fast clearance, and low production of brain metabolites in healthy mice^[1]. [11C]MODAG-005 (intravenous administration; single bolus injection) binds specifically to α-synuclein fibrils in rats with striatal injections^[1]. [11C]MODAG-005 (intravenous administration; single bolus injection) exhibits specific, pathology-associated binding to intracellular α-synuclein aggregates in α-SynA30P transgenic mice^[1]. [11C]MODAG-005 (intravenous administration; single bolus injection) exhibits favorable pharmacokinetic properties in healthy cynomolgus monkeys, including rapid brain uptake, rapid clearance, and detectable plasma metabolism^[1].

In Vitro, [3H]MODAG-005 exhibits subnanomolar binding affinity for recombinant human α-synuclein fibrils, shows 36-fold lower affinity for tau fibrils and over 100-fold lower affinity for Aβ1-42 fibrils, with an MAO-B IC₅₀ of 0.8 μM and no other relevant off-target binding^[1]. [3H]MODAG-005 binds specifically to α-synuclein pathology in post-mortem human multiple system atrophy (MSA) brain tissues, with a high-affinity binding site (Kd = 0.19 nM); it shows no specific binding in control brain tissues and does not bind to monoamine oxidase B (MAO-B) in MSA tissues^[1].

References:
[1]. Saw RS, et al. The PET tracer [11C]MODAG-005 targets alpha-synuclein aggregates in the brain. Sci Transl Med. 2026 May 27;18(851):eaec0813.