NCI Convenes Workshop on Dosimetry of Systemic Targeted Radiopharmaceutical Therapy (TRT)

Systemic targeted radiopharmaceutical therapy (TRT) is an evolving and promising modality of cancer treatment. It provides a unique means to efficiently eradicate disseminated tumor cells and small metastases before they are detectable by currently available methods. By administering the treatment planning (trace-labeled) dose and determining the patient's residence time (how long the radionuclide is retained in the body), the therapeutic dose can be precisely adjusted to maximize the therapeutic effect and minimize toxicity.

The paradigm of utilizing a targeted drug with a patient-specific dose should become routine as targeted therapies are further developed with better assays to directly measure drug levels. Although whole-body dosimetry is routinely applied for TRT, the patient-specific maximally tolerated therapeutic radiation dose should be used to maximize efficacy while minimizing organ and bone marrow toxicity. To promote collaboration among academic research and clinical centers, industry, and government agencies that could positively impact this field, staff from DCTD's Radiation Research Program, together with members of the TRT Dosimetry Working Group, planned and convened a workshop on April 19-20, 2018. Attendees from these institutions discussed the scientific, practical, and regulatory aspects of TRT dosimetry.

The workshop presentations and discussion included the following topics:

• Status of TRT
• TRT dosimetry methods and approaches that are:
  • Currently applied
  • Available
  • Under development
  • Desired
• Good dosimetry practices
• Dosimetry needs and methods for radiopharmaceuticals containing the following radioisotopes: I-131, Y-90, Lu-177, Sm-153, Ra-223, Pb-212, Ac-225, Bi-212, At-211, and th-227

The workshop participants identified specific needs to facilitate successful implementation of TRT in clinical practice, including:

• Standardization and validation tools and strategies to optimize accuracy and precision of TRT
• Development of clinical workflows and dosimetric and treatment planning tools
• Implementation of appropriate methods for reporting of radiation dose delivered to tumor and normal tissues, and assessment of radiation biology equivalence
• Overcoming barriers to adaptation of new radiopharmaceuticals for clinical trials
• Implementation of quantitative imaging methods for patient-specific dosimetry and treatment planning
• Development of in vitro tumor and animal models that could provide meaningful insight for dosimetric understanding of TRT