99mTc-Glu-c(RGDyK)-Bombesin SPECT Can Reduce Unnecessary Biopsy of Masses That Are BI-RADS Category 4 on Ultrasonography.

Abstract

Masses that, on ultrasonography, are category 4 according to the Breast Imaging Reporting and Data System (BI-RADS) represent possible malignancy, and a biopsy is recommended. This study explored the value of (99m)Tc-Glu-c(RGDyK)-bombesin ((99m)Tc-RGD-bombesin) in reducing unnecessary biopsy of these masses. Ninety women with a BI-RADS 4 mass on ultrasonography were enrolled in this study to undergo breast SPECT using (99m)Tc-RGD-bombesin. The images were independently interpreted using qualitative visual and semiquantitative analyses. The final diagnosis was based on histopathologic examination of surgically excised or percutaneous biopsy specimens. Fractions of the samples were immunohistochemically analyzed to evaluate expression of integrin αvβ3 and gastrin-releasing peptide receptor (GRPR). The receptor-positive group was further divided into 3 subgroups (GRPR(+)/αvβ3 (+), GRPR(+)/αvβ3 (-), and αvβ3 (+)/GRPR(-)). Ninety-four masses (22 malignant and 72 benign) were confirmed by histopathologic examination. On qualitative analysis, 20 of the malignant masses showed high (99m)Tc-RGD-bombesin accumulation and 48 of the benign masses showed no (99m)Tc-RGD-bombesin accumulation. The optimal cutoff for qualitative analysis was a score of 2. Semiquantitative analysis revealed that 20 of the malignant masses and 16 of the benign masses had a relatively high tumor-to-normal-tissue ratio (T/N). The optimal cutoff was a T/N of 2.26. The mean T/N was higher for malignant masses than for benign masses (3.17 ± 0.86 vs. 1.89 ± 0.71, P < 0.05). T/Ns did not differ among the 3 subgroups (P > 0.05). The areas under the receiver-operating-characteristic curves for the qualitative and semiquantitative analyses were 0.788 and 0.865, respectively, and the overall diagnostic performance did not significantly differ between these analyses (P > 0.05). (99m)Tc-RGD-bombesin SPECT can differentiate benign from malignant BI-RADS 4 masses with high specificity. Further study of the application of this test to clinical breast cancer appears warranted.