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¹⁸⁶Re-HEDP in the Treatment of Patients with Inoperable Osteosarcoma

¹ Institute of Nuclear Medicine, University College Hospital, London, United Kingdom; and ² Meyerstein Institute of Oncology, University College Hospital, London, United Kingdom

Correspondence: For correspondence or reprints contact: Jamshed B. Bomanji, MBBS, PhD, Institute of Nuclear Medicine, University College Hospital, 5th Floor, 235 Euston Rd., London NW1 2 BU, U.K. E-mail: jamshed.bomanji{at}uclh.nhs.uk

The aim of this study was to examine the safety and efficacy of ¹⁸⁶Re-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 ¹⁸⁶Re-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 ¹⁸⁶Re-HEDP treatment. The mean tumor dose delivered with ¹⁸⁶Re-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 ¹⁸⁶Re-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. Conclusion: 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 ¹⁸⁶Re-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.

Key Words: ¹⁸⁶Re-HEDP • therapy • inoperable osteosarcoma • external-beam radiotherapy

COPYRIGHT © 2006 by the Society of Nuclear Medicine, Inc.

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