Day Two

• Visualizing biodistribution, uptake, and clearance with PET/SPECT
• Linking preclinical imaging data to dosimetry optimization
• Accelerating efficacy predictions through early PK insights

• Combining imaging and PK data to refine dose prediction
• Accounting for isotope- and target-specific considerations
• Streamlining methods for more efficient and accurate dosimetry

• Profiling biomarkers to reveal individual treatment responses, helping identify which patients are most likely to benefit from therapy
• Tailoring dosimetry for each patient to optimize efficacy and safety by adjusting doses based on personalized radiation exposure
• Speeding early development through data-driven personalization, using patient-specific information to guide decision-making and trial design

• Exploring DNA damage synergy between alpha/beta emitters and DDR inhibitors to amplify tumor cell killing
• Optimizing preclinical combination timing and sequencing to maximize efficacy while minimizing toxicity
• Identifying biomarkers to guide patient selection and predict responsiveness in combination strategies

• Characterizing RLT-induced immune modulation and its role in tumor sensitization and resistance
• Evaluating preclinical combinations of RLT with immune checkpoint inhibitors, CAR-T cells, and emerging immunotherapies
• Leveraging synergistic immune-radiobiological mechanisms to enhance depth and durability of response

• Balancing toxicity and efficacy: minimizing radiopharmaceutical dose while enhancing tumor kill
• Timing combination therapies: strategies for preclinical-to-clinical translation
• Selecting patients using biomarkers to match optimal RLT combinations with tumor and TME characteristics

• Identifying molecular, imaging, and circulating biomarkers that explain interpatient variability in response to ^177Lu-PSMA-617
• Correlating biomarker profiles with treatment response, resistance, and toxicity to refine patient selection
• Informing treatment sequencing and personalization strategies to optimize outcomes in mCRPC

• Characterizing early hematologic effects and dose-limiting toxicities using Phase 0 microdosing studies
• Dissecting mechanisms of bystander irradiation contributing to bone marrow exposure and cytopenias
• Informing dose escalation and safety margins for subsequent first-in-human and Phase 1 trials

• Characterizing mechanisms of renal and hepatic injury associated with alpha-emitting radioligand therapies
• Evaluating clinical and molecular strategies to reduce off-target organ exposure and cumulative toxicity
• Guiding dosing, scheduling, and patient monitoring to enable safer clinical application of novel alpha emitters

• Interpreting current FDA guidance on dose selection, escalation, and optimization for radioligand therapies
• Integrating pharmacokinetics, biodistribution, and safety data to refine patient-specific dosing strategies
• Applying regulatory best practices to design trials that balance therapeutic efficacy with minimization of off-target toxicity

• Challenging traditional 3+3 dose escalation procedures for RLT dosing, given their limited efficiency and ability to capture cumulative radiation effects
• Comparing dose escalation versus dose accumulation strategies in radiopharmaceutical therapy, with emphasis on safety, exposure, and dose-response characterization
• Incorporating dosimetry-informed or model-based designs into early RLT trials to better link delivered radiation dose with safety and efficacy outcomes

• Comparing personalized versus standard dosimetry approaches and their impact on patient safety and treatment efficacy
• Assessing operational, logistical, and cost challenges of implementing individualized dosimetry at scale
• Evaluating strategies to balance precision treatment with practical feasibility in widespread RLT adoption

• Considering high-impact areas for automation to improve batch consistency, reduce human error, and enhance operator safety
• Discussing integration challenges in retrofitting automation into facilities while maintaining GMP compliance
• Evaluating the return on investment, the benefits and the challenges of automation, including improved scalability and consistency versus difficulties like maintenance requirements

• Evaluating site selection, building integrity, and layout to safely accommodate shielding, specialized equipment, and future technology upgrades
• Optimizing workflows, compartmentalization, and contamination controls to maximize operational efficiency while maintaining strict safety standards
• Implementing advanced containment, automation, and ventilation systems to minimize radiation exposure, enhance staff well-being, and support long-term productivity

• Exploring how leveraging radiopharmacies for therapeutic preparation can extend regional coverage, reduce time-to-treatment for short-lived isotopes, and ease pressure on centralized manufacturing
• Understanding regulatory and operational restrictions in compounding manufacturing and radiopharmacy roles
• Discussing strategic partnerships with national pharmacy networks to improve batch consistency, point-of-care readiness, and public/physician trust in decentralized delivery

• Identifying the importance of measuring potency of every step of production
• Navigating challenges with analyzing potency at different stages
• Maximizing analytical techniques to ensure potency remains consistent through the production cycle

Session Reserved for Novartis

• Exploring what the release criteria for product purity is, including identifying acceptable limits for impurities and relevant quality attributes.
• Evaluating how to prove product purity using appropriate analytical techniques and risk-based testing strategies
• Optimizing analytical methods to show product purity in accordance with release criteria, ensuring accuracy, sensitivity, and reproducibility

• Understanding challenges associated with intermediates characterization, particularly those driven by short half-lives
• Navigating regulatory challenges associated with changes in manufacturing processes, including demonstrating comparability and justifying revised control strategies to regulators
• Cost/benefit analysis of improved processes, balancing upfront investment against improved batch consistency, reduced deviations, and more reliable quality readouts