Exploring the theranostic role of Lu-177 herceptin in HER2 expressing breast cancer: Preliminary studies on comparison with F-18-FDG PET/CT

Objectives: Herceptin is an anti HER2 antibody and often used for the treatment of HER2 primary and metastatic disease. Lu-177 herceptin may prove as a potential therapeutic option for the metastatic disease. F-18-FDG PET/CT is very useful in evaluating the extent of disease. In this prospective study Lu-177 herceptin was explored for targeting HER2 expressing breast cancer and associated metastatic lesions that were picked up by F-18-FDG PET/CT. Methodology: The radioimmunoconjugate Lu-177-Herceptin was developed in-house in hospital radiopharmacy lab. The preparation was standardized as clinical grade by performing complete quality control and preclinical evaluation. Clinical evaluation was carried out after obtaining clearance from the institute ethics committee and written informed consent from the patients for participation in the study. Patients with biopsy proven breast cancer (n=16; HER2 positive and negative) were administered Lu-177-Herceptin (185-740 MBq). The total protein dose delivered was kept constant (25 mg). All the patients had undergone F-18-FDG PET/CT before undergoing Lu-177-Herceptin study and had at least one F-18-FDG avid lesion. Planar and SPECT/CT imaging was performed on day 5/7 post administration of Lu-177-Herceptin. The images were compared to the F-18-FDG PET/CT images to evaluate the targeting potential of Lu-177-Herceptin for the HER2 lesions. The tumor to background ratio was determined from planar images using region of interest (ROI) analysis. Results: The developed radioimmunoconjugate Lu-177-herceptin had radiochemical purity >95%. The in-house preparations were sterile (on broth incubation) with endotoxin content within permissible limits (<175 EU/V). Lu-177-herceptin imaging showed no localization in all HER2 negative patients (n=4), having F-18-FDG avid lesions. Corresponding to the F-18-FDG uptake localization of Lu-177-Herceptin was observed in primary lesions in 5 out of 11 HER2 positive patients on planar and SPECT/CT images, 1 patient had recurrent lung metastases observed on planar and SPECT/CT images. SPECT/CT, 5 patients had FDG avid metastatic disease. Lu-177-herceptin localization was observed in 3 out of 10 metastatic lesions on whole body image and 8 out of 10 metastatic lesions (including skeletal mets and lymph nodes) on SPECT/CT. Two metastatic lesions were not visualized owing to the low resolution of SPECT/CT. The average maximum tumor to background ratio for primary lesions was 3.9 and for metastatic lesions was 3.2. No non-specific tracer localization was observed. Conclusion: This study concluded that Lu-177-herceptin may hold theranostic potential for use in radioimmunotherapy of HER2 metastatic breast cancer.

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