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Development of Lu-177-trastuzumab for radioimmunotherapy of HER2 expressing breast cancer and its feasibility assessment in breast cancer patients
- Source :
- International Journal of Cancer. 140:938-947
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- HER2/neu is over expressed in 20–25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu-177-trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA-conjugated trastuzumab was optimized using Lu-177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed. A preliminary pilot study was conducted on breast cancer patients (n = 6 HER2 positive and n = 4 HER2 negative) to evaluate the ability of Lu-177-trastuzumab for HER2 specific tumor targeting. The conjugates were efficiently labeled with Lu-177 with high radiochemical purity (up to 91%) and specific activity (6–13 µCi/µg). Lu-177-trastuzumab was stable up to 12 hr post labeling. The radioimmunoassay demonstrated good antigen binding ability and specificity for HER2 receptor protein. The patient studies showed the localization of Lu-177-trastuzumab at primary as well as metastatic sites (HER2 positive) in the planar and SPECT/CT images. No tracer uptake was observed in HER2 negative patients that indicated the specificity of Lu-177-trastuzumab. The study demonstrated that in-house developed Lu-177-trastuzumab has specific targeting ability for HER2 expressing lesions and may in future become a palliative treatment option in the form of targeted radionuclide therapy for disseminated HER2 positive breast cancer.
- Subjects :
- Oncology
Cancer Research
medicine.medical_specialty
Pathology
Poor prognosis
Sterility
medicine.medical_treatment
030218 nuclear medicine & medical imaging
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Trastuzumab
Internal medicine
medicine
DOTA
skin and connective tissue diseases
neoplasms
business.industry
Radioimmunoassay
medicine.disease
chemistry
030220 oncology & carcinogenesis
Radioimmunotherapy
Specific activity
business
medicine.drug
Subjects
Details
- ISSN :
- 00207136
- Volume :
- 140
- Database :
- OpenAIRE
- Journal :
- International Journal of Cancer
- Accession number :
- edsair.doi...........678baf62c4402126a3d958fec7b2554b