RT Journal Article
SR Electronic
T1 Biokinetic Modeling and Dosimetry for Optimizing Intraperitoneal Radioimmunotherapy of Ovarian Cancer Microtumors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 594
OP 600
DO 10.2967/jnumed.115.167825
VO 57
IS 4
A1 Stig Palm
A1 Tom Bäck
A1 Börje Haraldsson
A1 Lars Jacobsson
A1 Sture Lindegren
A1 Per Albertsson
YR 2016
UL http://jnm.snmjournals.org/content/57/4/594.abstract
AB A biokinetic model was constructed to evaluate and optimize various intraperitoneal radioimmunotherapies for micrometastatic tumors. The model was used to calculate the absorbed dose to both anticipated microtumors and critical healthy organs and demonstrated how intraperitoneal targeted radiotherapy can be optimized to maximize the ratio between them. Methods: The various transport mechanisms responsible for the biokinetics of intraperitoneally infused radiolabeled monoclonal antibodies (mAbs) were modeled using a software package. Data from the literature were complemented by pharmacokinetic data derived from our clinical phase I study to set parameter values. Results using the β-emitters 188Re, 177Lu, and 90Y and the α-emitters 211At, 213Bi, and 212Pb were compared. The effects of improving the specific activity, prolonging residence time by introducing an osmotic agent, and varying the activity concentration of the infused agent were investigated. Results: According to the model, a 1.7-L infused saline volume will decrease by 0.3 mL/min because of lymphatic drainage and by 0.7 mL/min because of the transcapillary convective component. The addition of an osmotic agent serves to lower the radiation dose to the bone marrow. Clinically relevant radioactivity concentrations of α- and β-emitters bound to mAbs were compared. For α-emitters, microtumors receive high doses (>20 Gy or 100 Sv [relative biological effect = 5]). Since most of the tumor dose originates from cell-bound radionuclides, an increase in the specific activity would further increase the tumor dose without affecting the dose to peritoneal fluid or bone marrow. For β-emitters, tumors will receive almost entirely nonspecific irradiation. The dose from cell-bound radiolabeled mAbs will be negligible by comparison. For the long-lived 90Y, tumor doses are expected to be low at the maximum activity concentration delivered in clinical studies. Conclusion: According to the presented model, α-emitters are needed to achieve radiation doses high enough to eradicate microscopic tumors.