{"artifact":{"id":"experiment-exp-wiki-experiments-tdp43-pet-ligand-development","artifact_type":"experiment","entity_ids":null,"title":"TDP-43 PET Ligand Development for FTD and ALS","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"wiki","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.902764Z"},"summary":"# TDP-43 PET Ligand Development for FTD and ALS\n## Background and Rationale\n# TDP-43 PET Ligand Development for FTD and ALS\n\nFrontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) represent devastating neurodegenerative diseases with substantial clinical and pathological overlap. Approximately 50% of FTD cases demonstrate TDP-43 proteinopathy as the primary pathological hallmark, while the remaining cases feature tau or FUS inclusions. Similarly, ALS presents with TDP-43 pathology","entities":{"genes":["TDP"],"diseases":["ALS"]},"model_system":"human","_schema_version":1,"experiment_type":"clinical","primary_outcome":"Validate TDP-43 PET Ligand Development for FTD and ALS","methodology_notes":"**Phase 1: Ligand Synthesis and In Vitro Validation (Months 1-6)**\n• Synthesize candidate TDP-43 PET ligands based on structural analysis of TDP-43 aggregates\n• Perform autoradiography on post-mortem brain tissue from FTLD-TDP (n=20), FTLD-tau (n=20), and control subjects (n=10)\n• Conduct binding affinity assays using recombinant TDP-43 aggregates (Kd determination)\n• Evaluate ligand selectivity against tau, α-synuclein, and amyloid-β aggregates\n• Assess blood-brain barrier penetration using in vitro models\n\n**Phase 2: Preclinical PET Imaging (Months 7-12)**\n• Radiolabel lead compounds with [¹¹C] or [¹⁸F] (n=3-5 ligands)\n• Perform biodistribution studies in healthy rodents (n=6 per ligand)\n• Conduct PET imaging in transgenic TDP-43 mouse models (n=8-10 per group)\n• Evaluate pharmacokinetics, brain uptake, and retention patterns\n• Perform ex vivo autoradiography correlation with PET signal\n\n**Phase 3: Human Safety and Dosimetry (Months 13-18)**\n• Conduct Phase I safety study in healthy ","replication_status":"replicated","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.902769","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID 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