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2 minute read
Antibody-drug conjugates (ADCs) have transformed oncology by combining targeted delivery with potent cytotoxic payloads. But traditional preclinical studies, focused on tumor growth inhibition, often leave blind spots in understanding how these complex molecules behave in the body. That’s where radiolabeling changes the game.
In our recent webinar, Radiotracers and ADC Targeting: Scientific Insights for In Vivo Validation and Clinical Transition, experts Dr. Denis R. Beckford-Vera (Champions Oncology) and Dr. Shankar Vallabhajosula (Weill Cornell Medicine, Convergent Therapeutics) unpacked the science and strategy behind using radiotracers to generate decision-driving data for ADC development.
Why Radiolabeling Matters for ADCs
Unlike unconjugated antibodies, ADCs can vary significantly in pharmacokinetics, biodistribution, and biotransformation depending on conjugation methods, linker chemistry, and payload properties. These factors directly influence efficacy and safety.
Radiolabeling both the antibody and/or payload enables you to:
- Quantify tissue distribution across the whole body
- Assess target engagement in tumors versus off-target organs
- Predict efficacy earlier in development
- Measure payload release and clearance for linker optimization
Key Takeaways from the Webinar
1. Dual Radiolabeling Reveals the Full Picture
By attaching one isotope to the antibody (e.g., Zr-89) and another to the payload (e.g., I-131), researchers can simultaneously track both components without signal interference. This approach reveals where the conjugate stays intact and where the payload is released, a critical insight for linker stability and safety profiling.
2. Imaging as a Predictor of Response
Molecular imaging with Zr-89–labeled ADCs has shown that tumor uptake patterns can predict which preclinical models respond to therapy. In responsive models, tumor-to-blood ratios are higher and sustained, while non-responsive models show uptake similar to non-specific controls.
3. Dual-Mechanism Therapeutic Potential
Pairing a radiolabeled antibody with a chemotherapeutic payload in a single ADC can produce additive or even synergistic anti-tumor effects, as demonstrated with Lu-177 + MMAE combinations.
4. Translating Preclinical Insight to the Clinic
In a HER3-targeting immuno-PET study, Zr-89–labeled antibodies were used to measure dose-dependent target engagement in patients. Imaging revealed saturable tumor uptake at higher mass doses, confirming target specificity and informing dose optimization strategies—insights not possible from biopsy alone.
The Champions Oncology Advantage
Champions Oncology integrates radiochemistry, in vivo imaging, biodistribution, and PDX model expertise into a streamlined workflow. This enables ADC developers to:
- Validate tumor targeting in clinically relevant models
- Quantify on-target and off-target uptake with precision
- Generate high-quality biodistribution and PK data to support IND submissions and partner discussions
- Ensure secure isotope supply for uninterrupted studies
Watch the Full Webinar
The blog you’re reading is just the highlights. In the full webinar, Radiotracers and ADC Targeting: Scientific Insights for In Vivo Validation and Clinical Transition, Dr. Beckford-Vera and Dr. Vallabhajosula dive into:
- Radiochemistry techniques for antibodies and payloads
- Case studies from approved and experimental ADCs
- Isotope selection and chelation strategies
- Translational use cases bridging preclinical and clinical studies
Watch the full recording to see how radiolabeling can de-risk your ADC program, accelerate timelines, and improve the odds of clinical success.
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