Simulated Radiation Dosimetry Models After Intraventricular and Intralumbar Injection of Radiopharmaceuticals

Radiation absorbed doses from intraventricular and intralumbar administration of 14 available radiopharmaceuticals with the potential to treat leptomeningeal metastasis (LM) are examined. Compartmental biokinetic models are employed to simulate human cerebral spinal fluid (CSF) flow and estimate normalized number of disintegrations (residence times) in the various compartments containing CSF and to estimate the fraction of the injected radiopharmaceutical that reaches the systemic circulation. Anthropomorphic radiation transport models are employed along with the residence times to determine absorbed doses to the CSF spaces, normal organs, and tissues from the activity in the CSF compartments, as well as depth dependent absorbed doses to the tissues immediately adjacent to the CSF compartments. Radiation absorbed dose to the normal organs and tissues resulting from radiopharmaceutical reaching the systemic circulation is determined using published dosimetry data. Several variations of assumed CSF transport are evaluated, including inadvertent stasis in the ventricle or lumbar spine. The resultant absorbed doses and dose rates in the CSF spaces can be utilized to evaluate and compare potential efficacy, and the absorbed doses in the normal organs and tissues can be used to evaluate and compare potential toxicity. Results of these theoretical predictive simulations allow for preliminary evaluation of the best radiopharmaceuticals for LM therapy. They may also enhance future design of optimal intrathecal radionuclide LM therapy strategies.