Unravelling the Potential of Lutetium-177 Labeled Pertuzumab: Targeting HER 2 Receptors for Theranostic Applications

Abstract

<h2>ABSTRACT</h2><h3>Purpose</h3> Pertuzumab, a humanized antibody against HER2 receptors has shown promising results in combination with trastuzumab and docetaxel for the neoadjuvant treatment of patients with HER2-positive breast cancer. The aim of the present study was to demonstrate the potential of <b>[</b>¹⁷⁷Lu]-Lu-DTPA-pertuzumab for targeting HER2 positive tumors. Comparative studies with <b>[</b>¹⁷⁷Lu]-Lu-DTPA-trastuzumab and synergism in presence of cold trastuzumab was also envisaged. <h3>Methods & Materials</h3> Pertuzumab and trastuzumab were conjugated with p-NCS-CHX-A''-DTPA and radiolabeled with Lutetium-177. The stability of the formulations was assessed and <i>in-vitro</i> binding parameters (immunoreactivity, saturation and competitive binding) were examined in HER2 overexpressing and HER2 negative cell lines. SPECT imaging studies were performed in SCID mice bearing HER2 positive tumors. <h3>Results</h3> <b>[</b>¹⁷⁷Lu]-Lu-DTPA-pertuzumab and trastuzumab could be prepared with >95% radiochemical purity (% RCP). <i>In-vitro</i> binding studies revealed high affinity and specificity of the formulations towards HER2 receptors. Specific tumor uptake of <b>[</b>¹⁷⁷Lu]-Lu-DTPA-pertuzumab in HER2 positive tumors was observed by SPECT imaging studies in tumor bearing mice, comparable to <b>[</b>¹⁷⁷Lu]-Lu-DTPA-trastuzumab. Significant retention of the formulations was observed in the tumor for up to 120 h. The studies also showed enhanced uptake of <b>[</b>¹⁷⁷Lu]-Lu-DTPA-pertuzumab in the presence of cold trastuzumab in HER2 positive tumors. <h3>Conclusions</h3> The present study revealed significant uptake of both ¹⁷⁷Lu labeled pertuzumab and trastuzumab in HER2 positive tumors. Further studies are warranted to determine efficacy of these formulations against tumor growth for confirming their potential as effective radioimmunotheranostic agents. Increase in uptake of radiolabeled pertuzumab in presence cold trastuzumab provides an avenue for more effective radionuclide imaging and therapy of HER2 positive tumors.