Preclinical data published in Nature Communications characterize AC Immune’s fluorine-18–labeled TDP-43 PET tracer, ACI-19626, showing high affinity for pathological TDP-43 aggregates with minimal binding to physiological TDP-43, strong selectivity over Abeta, Tau, and alpha-synuclein, no detectable off-target activity across a >100 target panel, and favorable non-human primate pharmacokinetics with rapid brain uptake and fast, complete washout in the absence of target—properties that support low background signal in healthy controls.
The core development: AC Immune has advanced ACI-19626 into an ongoing Phase 1 study, with an initial readout expected in Q4 2025. The Nature Communications paper represents the first full characterization of a TDP-43 PET tracer with a profile suitable for human imaging, aimed at enabling in vivo detection of a pathology implicated in ALS, FTD, and LATE, and commonly present as co-pathology in Alzheimer’s and Parkinson’s disease. The tracer is built on the company’s Morphomer platform and uses an F-18 isotope, aligning with existing PET site infrastructure.
Strategically, this is an enabling-asset play more than a stand-alone diagnostic bet. TDP-43 has remained a blind spot for precision medicine because of the absence of validated imaging tools; a reliable tracer could reshape trial architecture across multiple neurodegenerative programs by reducing etiologic noise and enriching for patients with the target pathology. For AC Immune, the tracer also complements its misfolded-protein therapeutic pipeline, creating optionality for target engagement readouts, pharmacodynamic assessment, and potentially a companion or codevelopment path with internal or partnered agents. The move also reflects a broader shift in neurodegeneration R&D toward pathology-confirmed inclusion criteria and objective biomarkers, following lessons from amyloid and tau programs.
Operationally, sponsors gain a route to reduce heterogeneity and screen failures in ALS/FTD studies, where clinical phenotypes overlap and biofluid assays remain inconsistent. CROs and imaging core labs should anticipate demand for centralized reads, kinetic modeling, SUVR standardization, and cross-scanner harmonization, with F-18 logistics requiring regional radiopharmacy coordination but avoiding the tighter constraints of C-11 tracers. Research sites with PET capacity may see increased screening volumes and protocol complexity, including investigational radiotracer workflows and potential post-mortem correlation substudies. Regulators will likely focus on neuropathology concordance, test-retest reliability, regional binding patterns consistent with disease biology, and analytical validation sufficient for biomarker qualification across indications.
The next checkpoint is whether Phase 1 demonstrates clean dosimetry and safety alongside robust brain kinetics, low white-matter and choroid plexus signal, and measurable target-to-background contrast in patients versus healthy controls. Evidence of regional binding in ALS and FTD consistent with known TDP-43 distribution, plus correlation with biofluid measures, would strengthen the case for qualification and multicenter rollout. Risks include unforeseen in vivo off-targets, inadequate signal-to-noise in early disease, quantification challenges across scanners, and the need for post-mortem validation to underpin regulatory acceptance. Watch for AC Immune to outline a multicohort strategy spanning ALS, FTD, and AD co-pathology, announce imaging-network partnerships for tracer supply and central reads, and pursue biomarker-qualification pathways that could make TDP-43 PET an inclusion and pharmacodynamic standard in next-wave neurodegeneration trials.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
