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The 2026 PSMA & Beyond Conference
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| Challenges of Radioligand Therapy |
| The Expanding Theranostic Dream: From Hype to Hard Truths
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| Michael Hofman, MBBS
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| Michael Hofman tempered theranostics hype with TheraP ph2 realities: 177Lu-PSMA-617 beat cabazitaxel in post-docetaxel mCRPC for PSA50, rPFS, ORR and PROs, but lacked OS benefit due to crossover and taxane superiority at preventing new mets despite tumor shrinkage. Variable responses, tumor heterogeneity, dosimetry inconsistencies (<10Gy non-responders), and 177Lu's short beta path underscore limitations; "Hofman's Hierarchy" ranks iodine > PSMA/DOTATATE > zombies.
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| Renal Toxicity Associated with PSMA Targeted Therapy
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| Inès Camille Azrour, PharmD
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| Inès Camille Azrour detailed PSMA-targeted therapy's renal risks via proximal tubule PSMA expression and megalin-cubilin reuptake, leading to radiation injury (alpha/beta/Auger) and phases: acute kidney injury (days 2+), acute kidney disease, chronic kidney disease, with VISION showing low late toxicity.
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| Long-Term Marrow Toxicity: Rates and Risk Factors
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| Daniel Childs, MD
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| Daniel Childs highlighted 177Lu-PSMA-617 marrow risks: anemia in phase 3 trials, real-world therapy-related myeloid neoplasms in Mayo Clinic and Peter MacCallum series, driven by radioligand-selected clonal hematopoiesis with PPM1D and TP53 dominance in TheraP analysis. Calls for prospective clonal hematopoiesis tracking and radiogenomic risk-adaptation to mitigate cytopenias and myeloid neoplasms in earlier settings.
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| Clinical Development |
| How PCWG4 Impacts Future Trials
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| Michael Morris, MD
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| Michael Morris explained PCWG4's shift to mechanistic disease framing (dropping "castration," emphasizing prior AR-directed therapy), genotype/phenotype/imaging classifiers, and rPFS as interim endpoint validated by COU-302/PREVAIL/VISION OS correlations. PCWG4's "Rule of 5" refines post-flare rPFS, incorporates PSMA PET, with independent reporting per modality. Cautions PSMA-only MFS; take-homes: new nomenclature, safer rPFS without timing change, PSMA integration for bone/lung/nodal (Rule 5)/visceral progression.
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| Developing Novel Radioligands 2 |
| Initial Experience with APC3
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| Philipp Backhaus, MD
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| Philipp Backhaus presented initial ACP3-targeted theranostics, tracing its biomarker history from 1950 to OncoACP3 in 2024, with sipuleucel-T approval bridging early developments. In a 2025 first-in-human study, 68Ga-OncoACP3-DOTA PET showed low salivary/kidney uptake vs high 18F-PSMA-1007, comparable SUVmax in localized/metastatic PCa, and superior detection in 11/25 vs 8/25 pairs. First-in-human 177Lu-OncoACP3 DOTA therapy data signals emerging RLT potential with favorable biodistribution.
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| Does FAP Have a Future: Pro
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| Wolfgang Fendler, MD
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| Wolfgang Fendler argued for FAP's theranostic future, highlighting its high expression in sarcoma/GI tumors as an ideal stromal target, with [68Ga]Ga-FAPI-46 PET showing 90% PPV for FAP+ tumors in a 2025 ph2 trial. 90Y-FAPI-46 RLT achieved 48% DCR in 30 sarcoma patients, while emerging 161Tb-FAPI dimer optimizes dosimetry vs 90Y. Next-gen ligands like 177Lu-PNT3090, FAMI-mFS, 177Lu-OncoFAP-23, and 177Lu-/225Ac-RTX2358 enhance targeting, positioning FAP for disease stabilization/regression.
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| Does FAP Have a Future: Con
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| Lena Unterrainer, MD
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| Lena Unterrainer argued against FAP's theranostic viability due to poor tumor retention, low absorbed doses vs approved agents like PSMA/DOTATATE, and lack of curative potential. Basket trials across heterogeneous entities/isotopes yield vast variability, entity-dependent/heterogeneous expression, and variable uptake, complicating evidence without a "clinical workhorse" scenario. Safety risks include 38% gr3/4 events; combos remain unproven amid "trial-and-error" isotope/disease matching and missing prospective data.
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