Planning time for peripheral blood stem cell infusion after high-dose targeted radionuclide therapy using dosimetry.

UNLABELLED: Myelotoxicity can be ameliorated by peripheral blood stem cell (PBSC) infusion. Continuous irradiation by radioactivity retained in the body after high-dose radioimmunotherapy can damage PBSCs if they are transfused too early. Previously, infusion time was predetermined using the radioactivity concentration in the blood. This study proposes to plan PBSC infusion time based on noninvasive dosimetry that considers damage of PBSCs during PBSC circulation and residence in organs with high radioactivity. METHODS: The method considers a time-varying distribution of PBSCs and radioactivity in tissues. Five breast cancer patients received (111)In-2IT-BAD-m170 for imaging, and 3 of the 5 received high doses of (90)Y-2IT-BAD-m170 therapy followed by PBSC infusion. (90)Y concentrations in tissues were extrapolated from quantitative imaging of (111)In, and (90)Y blood concentrations were determined from (90)Y in serial blood samples. The radiation dose to PBSCs was determined by time integration of the organ dose rate and PBSC distribution rate. The radiosensitivity of PBSCs was determined by measuring survival of granulocyte-macrophage colony-forming units with (90)Y in cell culture. RESULTS: The mean effective half-life of (90)Y within the imaging period (up to 6 d) was 3.7 d for liver, 2.4 d for spleen, 2.1 d for kidneys, 1.8 d for lungs, and 1.6 d for blood. The survival fractions of PBSCs in patients were determined as functions of the infusion time and the injected dose of (90)Y-2IT-BAD-m170. To achieve 90% PBSC survival rate for a 2.0-GBq injection dose, PBSC dosimetry suggested a time interval of 13 d after radioimmunotherapy for PBSC infusion. In contrast, the simple blood concentration method suggested an interval about 7 d for the same PBSC survival rate. In our clinical practice, an interval of 2 wk has been used and worked well. CONCLUSION: A noninvasive dosimetry method was developed for optimizing the time interval for PBSC infusion after high-dose radionuclide therapy. Our studies suggested that the PBSC dosimetry method was more effective than the blood concentration method in determining the optimal time to reinfuse PBSCs for radiopharmaceuticals that have much a higher activity concentration in organs than that in the blood.

Film dosimetry in the peripheral region using multiple sensitometric curves.

We present a method for applying film dosimetry to the peripheral region utilizing multiple sensitometric curves. There are many instances when the dose to the peripheral region outside the field edges is of clinical and/or research interest. Published peripheral dose data may be insufficient if detailed dose modeling is required, and in those cases measurements must be performed. Film dosimetry is an attractive approach for dose measurement in the peripheral region because it integrates dose, overcoming the low-dose-rate problem, and is time efficient, as it acquires an entire plan of data in a single exposure. However, film response increases at energies below approximately 300 keV. As the scattered photon spectrum changes with distance from the field edge, this increased film sensitivity causes changes in the film response along profiles perpendicular to the field edge. A single sensitometric curve is therefore no longer sufficient for accurate conversion of the optical density to dose. Our new method uses multiple sensitometric curves defined at increasing distances from the field edge. To convert an optical density profile, the dose at each point in the profile is defined as a linear combination of the doses calculated using the two sensitometric curves that bracket the point of interest. A single set of sensitometric curves derived at one field size and source-to-surface distance (SSD) can be applied to density profiles for other field sizes and SSDs. We verified our new method by comparison to ion chamber measurements using three different types of film. Agreement with chamber measurements was within 7%, or less than 2 mm in regions of high gradient, over a wide range of field sizes and SSDs.

Treatment planning for molecular targeted radionuclide therapy.

Molecular targeted radionuclide therapy promises to expand the usefulness of radiation to successfully treat widespread cancer. The unique properties of radioactive tags make it possible to plan treatments by predicting the radiation absorbed dose to both tumors and normal organs, using a pre-treatment test dose of radiopharmaceutical. This requires a combination of quantitative, high-resolution, radiation-detection hardware and computerized dose-estimation software, and would ideally include biological dose-response data in order to translate radiation absorbed dose into biological effects. Data derived from conventional (external beam) radiation therapy suggests that accurate assessment of the radiation absorbed dose in dose-limiting normal organs could substantially improve the observed clinical response for current agents used in a myeloablative regimen, enabling higher levels of tumor control at lower tumor-to-normal tissue therapeutic indices. Treatment planning based on current radiation detection and simulations technology is sufficient to impact on clinical response. The incorporation of new imaging methods, combined with patient-specific radiation transport simulations, promises to provide unprecedented levels of resolution and quantitative accuracy, which are likely to increase the impact of treatment planning in targeted radionuclide therapy.