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Prodrugs

Prodrugs

Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...

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Related Experiment Video

Updated: Jun 4, 2025

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

Published on: January 29, 2019

Localized In Vivo Prodrug Activation Using Radionuclides.

Jeremy M Quintana¹, Fangchao Jiang¹, Mikyung Kang¹

¹Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts.

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine

|January 3, 2025

Summary

This summary is machine-generated.

This study introduces Radionuclide-Induced Drug Engagement for Release (RAiDER), a novel method to activate chemotherapy drugs specifically at tumor sites using targeted radiation. RAiDER enhances cancer treatment efficacy by combining radiation and chemotherapy, minimizing side effects from off-target drug activation.

Keywords:

FAPI combination chemoradiotherapy radionuclide therapy theranostics

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Area of Science:

Nuclear Medicine
Radiopharmaceutical Therapy
Cancer Treatment

Background:

Targeted radionuclides offer molecular specificity for imaging and therapy.
Hypothesis: Local radionuclide energy can activate prodrugs at disease sites, avoiding systemic toxicity.
Development of Radionuclide-Induced Drug Engagement for Release (RAiDER) strategy.

Purpose of the Study:

To test the RAiDER strategy for localized delivery of combined radiation and chemotherapy.
To maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy.
To evaluate RAiDER's potential in cancer treatment.

Main Methods:

Screened radionuclides for activating a radiation-responsive caged monomethyl auristatin E (MMAE) prodrug.
Utilized TOPAS-nBio for radiobiology simulations.
Evaluated RAiDER in mouse cancer models using FAPI and PSMA agents with caged MMAE or exatecan, combined with biodistribution and clinical dosimetry.

Main Results:

RAiDER efficiency varied significantly across radionuclides (e.g., 99mTc > 111In > 177Lu).
Activated MMAE restored microtubule destabilization and increased cytotoxicity up to 2,600-fold.
RAiDER treatment in mice showed significantly delayed tumor growth compared to monotherapies, with high tumor-specific activated MMAE concentrations.

Conclusions:

RAiDER is compatible with various nuclear medicine radionuclides and shows potential for improved cancer therapy efficacy and safety.
The strategy effectively targets prodrug activation to tumors, minimizing off-target toxicity.
RAiDER broadens radiopharmaceutical capabilities for diverse therapeutic responses in disseminated malignancies.