title: Biological in situ dose painting for image-guided radiation therapy using drug-loaded implantable devices.
abstract: OBJECTIVE
  Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment.
  
  
  METHODS
  Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ("eluters"), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate (125)I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example.
  
  
  RESULTS
  Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for approximately 4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of "biologically equivalent doses" to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum.
  
  
  CONCLUSIONS
  Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.
authors.affiliation: Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cormack
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sridhar
authors.forename: W Warren
authors.initials: WW
authors.lastname: Suh
authors.forename: Anthony V
authors.initials: AV
authors.lastname: D'Amico
authors.forename: G Mike
authors.initials: GM
authors.lastname: Makrigiorgos
mesh_terms: D000465:Algorithms; D001918:Brachytherapy / Q000295:instrumentation* / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D019736:Prostheses and Implants; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D007457:Iodine Radioisotopes; D011838:Radiation-Sensitizing Agents