Research

Research

The Radionuclide Therapy and Dosimetry Research Lab is focused on modeling and dosimetry analysis of radionuclide therapy to support the translation of novel targeted radionuclide therapy strategies to the clinic.  The research is divided between laboratory studies and patient-specific dosimetry/radiobiological modeling studies. 

The laboratory studies are examining bismuth-213 and actinium-225, targeting of tumor.  Bismuth-213 decays with a 45.6 min half-life via a branched decay scheme leading to the emission of an 8.4 MeV alpha particle.  Actinitum-225 has a 10-day half-life and a decay scheme that leads to three alpha-particle emitting daughters.  Intact antibodies and immunoliposomes are being examined as carriers of these isotopes.  Pre-clinical studies are being performed using a transgenic, neu expressing breast cancer model (the neu-N model) and an ovarian carcinoma model.  Left cardiac injection of a syngeneic tumor cell line in the neu-N model leads to widespread metastases to bone, marrow, liver and spleen; bone metastases are osteolytic.  The target antigen, neu, is also expressed on normal organs.  This model is being used to investigate targeting of early breast cancer metastases using bismuth-213 in the presence of cross-reactive normal tissue.  IP injection of tumor cells in the ovarian carcinoma model leads to widespread metastases in the intraperitoneal cavity.  Liposomally entrapped actinium-225 targeting is being investigated using this model.  The development of metastatic disease in these models and also antibody and immunoliposomal targeting has been characterized by small animal imaging, including MRI, µPET, µSPECT/µCT and optical fluorescent imaging.

These pre-clinical studies are being performed in conjunction with pharmacokinteic and microdosimetric model development, validation and analysis.  In addition to the animal models, cell and spheroid dose-response studies are being used to provide data for model development and validation.  The objectives of this work are to provide the necessary pre-clinical data and analysis to translate alpha-emitter targeting of rapidly accessible metastatic disease to the clinic.

The clinical dosimetry studies are centered around the on-going development of 3D-ID (for 3D-Internal Dosimetry), a software package that accepts patient SPECT/CT or PET/CT images of radiopharmaceutical distribution and uses the information to estimate the spatial distribution of absorbed dose to normal organs and to tumors using point kernel convolution or Monte Carlo calculation.  Key objectives of this work are to improve the accuracy of absorbed dose estimates, incorporate radiobiological modeling and demonstrate a predictive relationship between absorbed dose and tumor response or normal organ toxicity.  The 3D-ID methodology has been applied to lymphoma (I-131-labeled anti-CD20 antibody) and thyroid cancer patients.  The Lab also provides clinical dosimetry support for I-131 therapy of thyroid cancer and for Bexxar and Zevalin therapy of Non-Hodgkins Lymphoma.