Tricom validating machine
First, it is important to recall that techniques in which a radionuclide is administered with therapeutic intent may or may not be targeted.
Methods for accurately assessing internalization into specific molecular targets were discussed for both research and clinical applications.He illustrated this principle with Bi-labeled monoclonal antibodies in mouse models of breast cancer metastases (18).As in other areas of TRT research, pairing preclinical studies with human studies allowed derivation of microscale absorbed dose without human autoradiography.Further, TRT can be paired with imaging and other techniques to predict delivery of therapeutic agents to tumor targets and normal organs before therapy administration and thus can be used to guide escalation protocols and treatment planning.These advantages make TRT especially promising in several cancers. Sgouros stressed the importance of reassessing dosimetry methods used in TRT, emphasizing the need to adopt methods specific to the therapy being used and geared to evaluating treatment efficacy and toxicity.He pointed to the general agreement of these methods and the advantages of 3D radiobiologic dosimetry in real-time treatment planning with patient-specific dosimetry and the potential for additional utility in combined-modality therapy (16). Sgouros reviewed considerations for α-particle dosimetry and characteristics that distinguish it from β-particle therapy.
For example, with α-particle therapy, the mean dose to any macroscopic target volume may not predict overall biologic effect (i.e., some cells may receive no dose, whereas others receive a high dose), such that total effective dose depends on the spatial distribution of activity relative to the target cell population.
TRT describes techniques in which one or more radionuclides, usually but not always incorporated into a conjugate or attached to a ligand, are administered with the goal of providing targeted therapy at the cellular or molecular level. George Sgouros reviewed the physics of TRT, highlighting the potential of TRT in cancer therapy and emphasizing the role of dosimetry in conducting phase I trials of novel radionuclide agents.
TRT delivery, which is not susceptible to the resistance mechanisms seen with chemotherapy, kills targeted cells instead of inhibiting growth or survival pathways and precludes adaptation.
Current dosimetry methods associated with and appropriate to radioimmunotherapy, for example, are often model-based methods for risk evaluation.
In general, these methods are not patient-specific, do not account for nonuniformity, and do not predict toxicity or efficacy. Sgouros recommended moving away from average absorbed dose, noting that a single absorbed dose volume is useful only if it successfully predicts biologic effects.
He recommended adoption of patient-specific, 3-dimensional (3D) dosimetry coupled with radiobiologic modeling, where 3D internal dosimetry has the advantages of being patient-specific, using accurate anatomy and activity data, calculating absorbed dose voxel by voxel, and providing output dose as a mean over a chosen volume or dose–volume histogram (9–11).