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


CONCLUSIONS
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.
Shen
Sui
S
Department of Radiation Oncology, Wallace Tumor Institute, University of Alabama at Birmingham, 1824 6th Avenue S., Birmingham, AL 35294, USA. sshen@uabmc.edu
DeNardo
Sally J
SJ
Richman
Carol M
CM
Yuan
Aina
A
Siantar
Christine Hartmann
CH
O'Donnell
Robert T
RT
Kroger
Linda A
LA
DeNardo
Gerald L
GL
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D036102:Peripheral Blood Stem Cell Transplantation; D016499:Radioimmunotherapy; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D013997:Time Factors; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C016467:Thomsen-Friedenreich antigen