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Lack of Correlation of Functional Scintigraphy with ^99mTechnetium-Methoxyisobutylisonitrile with Histological Necrosis following Induction Chemotherapy or Measures of P-Glycoprotein Expression in High-Grade Osteosarcoma¹

Departments of Pediatrics [R. G., R. S., M. D., E. C., L. H. W., P. A. M.], Nuclear Medicine [A. C. L., S. D. Y., S. M. L.], Pathology [C. A., A. G. H.], Radiology [D. P.], and Surgery, Orthopaedic Service [J. H. H.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021

In osteosarcoma, some studies have suggested P-glycoprotein expression is a prognostic factor. The clearance of ^99mtechnetium hexakis-2-methoxyisobutylisonitrile (^99mTc-MIBI) has been used in some tumor systems as an in vivo measure of P-glycoprotein-mediated efflux. In this study we explored the correlation between ^99mTc-MIBI clearance and histological necrosis following induction chemotherapy and P-glycoprotein expression in osteosarcoma. The primary tumors of 20 patients with high-grade osteosarcoma were imaged at diagnosis with ^99mTc-MIBI, and the uptake ratios and biological half-lives were calculated. P-Glycoprotein expression in the tumor tissue was determined immunohistochemically and by measuring mRNA expression of the multidrug resistance-1 gene. The histological necrosis following induction chemotherapy was assessed by the Huvos grading system. The biological half-life of ^99mTc-MIBI ranged from 1.4 to 52.5 h. Seven of the 20 tumor samples had a favorable extent of necrosis following induction chemotherapy. The ^99mTc-MIBI half-life and uptake ratio showed no correlation with histological necrosis following induction chemotherapy. The ^99mTc-MIBI half-life and uptake ratio did not correlate with either measure of P-glycoprotein expression. The results of this pilot study indicate that ^99mTc-MIBI imaging is not an effective predictor of histological necrosis following induction chemotherapy in high-grade osteosarcoma. ^99mTc-MIBI imaging did not correlate with measures of P-glycoprotein expression in the tumor tissue.

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