186Re-HEDP in the treatment of patients with inoperable osteosarcoma.
The aim of this study was to examine the safety and efficacy of (186)Re-hydroxyethylidene diphosphonate (HEDP) as an adjuvant to external-beam radiotherapy (EBRT) in the treatment of patients with osteosarcoma.


METHODS
Thirteen patients (9 male, 4 female; age range, 12-42 y) were treated with combination chemotherapy (standard U.K. protocol) and (186)Re-HEDP therapy (18.5 MBq/kg, intravenously), followed by EBRT. A full blood count; liver function test; and measurements of urea and electrolytes, glomerular filtration rate, and left ventricular function were performed on all patients before and after therapy. Tumor volume and composition were obtained from CT or MRI data. Dosimetric calculations were performed using the MIRD formalism.


RESULTS
Of the 13 patients, 1 is still under follow-up. The median survival time was 36 mo (range, 12-216 mo) from diagnosis and 5 mo (range, 1-60 mo) from the last (186)Re-HEDP treatment. The mean tumor dose delivered with (186)Re-HEDP was calculated to be 5.8 Gy (range, 0.5-16 Gy). CT and MRI revealed the tumors to have a complex structure, comprising "ossified," "partially calcified," and "soft-tissue" components. Posttherapy scans showed a heterogeneous distribution of (186)Re-HEDP in the tumor mass: Although the "soft-tissue" component showed minimal uptake of the therapeutic dose, the "ossified component" showed intense uptake. The 3 long-term survivors in whom tumor sterilization was achieved received calculated mean tumor doses in the range of 2.0-3.1 Gy, which was believed to be an underestimate of the actual tumor doses delivered.


CONCLUSIONS
This study indicates that a simple approach to tumor dosimetry based on mean tumor dose is inappropriate because it may underestimate the dose delivered to these heterogeneous tumors. The data also indicate that EBRT combined with a standard dose of 18.5 MBq/kg of (186)Re-HEDP does not provide a sufficient dose to achieve tumor sterilization. A dose estimation technique is required that is based on the determination of tumor dose at the individual voxel level and that is able to represent the heterogeneous uptake observed in these complex tumor structures with highly nonuniform composition. This, coupled with individualized dose escalation, may then achieve the goal of tumor sterilization.
Syed
Rizwan
R
Institute of Nuclear Medicine, University College Hospital, London, UK.
Bomanji
Jamshed
J
Nagabhushan
Nagesh
N
Kayani
Irfan
I
Groves
Ashley
A
Waddington
Wendy
W
Cassoni
Anna
A
Ell
Peter J
PJ
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001822:Body Burden; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002648:Child; D012968:Etidronic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000379:methods; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C101598:rhenium-186 HEDP; D012968:Etidronic Acid