title: Tumor dosimetry and response for 153Sm-ethylenediamine tetramethylene phosphonic acid therapy of high-risk osteosarcoma.
abstract: (153)Sm-ethylenediamine tetramethylene phosphonic acid ((153)Sm-EDTMP) therapy for osteosarcoma is being investigated. In this study, we analyzed the influence of (153)Sm-EDTMP administered activity (AA), osteosarcoma tumor density, mass, and the shape of the tumor on absorbed dose (AD). We also studied the biologic implication of the nonuniform tumor AD distribution using radiobiologic modeling and examined the relationship between tumor AD and response.
  
  
  METHODS
  Nineteen tumors in 6 patients with recurrent, refractory osteosarcoma enrolled in a phase I or II clinical trial of (153)Sm-EDTMP were analyzed using the 3-dimensional radiobiologic dosimetry (3D-RD) software package. Patients received a low dose of (153)Sm-EDTMP (37.0-51.8 MBq/kg), followed on hematologic recovery by a second, high dose (222 MBq/kg). Treatment response was evaluated using either CT or MRI after each therapy. SPECT/CT of the tumor regions were obtained at 4 and 48 h or 72 h after (153)Sm-EDTMP therapy for 3D-RD analysis. Mean tumor AD was also calculated using the OLINDA/EXM unit-density sphere model and was compared with the 3D-RD estimates.
  
  
  RESULTS
  On average, a 5-fold increase in the AA led to a 4-fold increase in the mean tumor AD over the high- versus low-dose-treated patients. The range of mean tumor AD and equivalent uniform dose (EUD) for low-dose therapy were 1.48-14.6 and 0.98-3.90 Gy, respectively. Corresponding values for high-dose therapy were 2.93-59.3 and 1.89-12.3 Gy, respectively. Mean tumor AD estimates obtained from OLINDA/EXM were within 5% of the mean AD values obtained using 3D-RD. On an individual tumor basis, both mean AD and EUD were positively related to percentage tumor volume reduction (P = 0.031 and 0.023, respectively).
  
  
  CONCLUSIONS
  The variations in tumor density, mass, and shape seen in these tumors did not affect the mean tumor AD estimation significantly. The tumor EUD was approximately 2- and 3-fold lower than the mean AD for low- and high-dose therapy, respectively. A dose-response relationship was observed for transient tumor volume shrinkage.
authors.affiliation: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Senthamizhchelvan
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hobbs
authors.forename: Hong
authors.initials: H
authors.lastname: Song
authors.forename: Eric C
authors.initials: EC
authors.lastname: Frey
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Elwood
authors.initials: E
authors.lastname: Armour
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
authors.forename: David M
authors.initials: DM
authors.lastname: Loeb
authors.forename: George
authors.initials: G
authors.lastname: Sgouros
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D064847:Multimodal Imaging; D009942:Organometallic Compounds / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D049268:Positron-Emission Tomography; D011874:Radiometry; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D012306:Risk; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C061972:samarium Sm-153 lexidronam