Background: Currently there are no FDA-approved imaging biomarkers capable of accurately identifying and quantitatively differentiating estrogen receptor (ER) status in breast cancer. The current preclinical study evaluated the ability of a Ga-68 positron emission tomography (PET) imaging biomarker and the analogous Lu-177 theranostic peptide construct to target and determine the status of ER expression.
Methods: Five human breast cancer cell line xenograft models were established in severe combined immunodeficiency mice. Western blot analysis confirmed the BB2r expression. The BB2r antagonist peptide construct was radiolabeled with Ga-68 and Lu-177, using fully automated radiochemistry labeling techniques. Pharmacokinetic, micro-SPECT/CT, and micro-PET/CT studies were performed.
Results: Pharmacokinetic studies confirmed that the Lu-177 construct targeted BB2r positive tissue in ER+ tumor xenograft models to a much greater extent than in ER- tumor xenograft models. In contrast, the ER-tumor xenografts demonstrated low initial uptake, followed by nearly complete washout from all tumor tissue within 24-hours after injection. The variances in tracer uptake by the tumor tissue correlated with BB2r expression via western blot analysis. Ga-68 micro-PET/CT data also correlated with the Lu-177 pharma-cokinetic studies, demonstrating visualization of BB2r+ tumor tissue with trends in standardized uptake values correlating directly with BB2r expression and ER status.
Conclusions: In summary, our study demonstrates selective tumor targeting for both a Ga-68 PET imaging biomarker and a Lu-177 theranostic agent in all breast cancer models studied. The Ga-68 PET SUV data suggest that PET imaging with this tracer or an analog of this tracer may have the potential to noninvasively differentiate ER status in vivo. Further studies are required involving an expanded panel of human cell lines and correlation with BB2 receptor expression/ER status obtained from biopsy data to confirm the potential validity of this finding.
