Dual Gastrin-Releasing Peptide Receptor and Integrin αvβ3 targeting PET/CT using ^sup 68^Ga-BBN-RGD in Patients with Breast Cancer

• Published in: The Journal of nuclear medicine (1978) Vol. 59; p. 55
• Main Authors: Zhang, Jingjing, Mao, Feng, Niu, Gang, Peng, Li, Lang, Lixin, Li, Fang, Ying, Hongyan, Wu, Huanwen, Zhu, Zhaohui, Chen, Xiaoyuan
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.05.2018
• Subjects: Accumulation; Biopsy; Body weight; Breast cancer; Breast carcinoma; Cancer; Cancer therapies; Computed tomography; Correlation; Diagnosis; ErbB-2 protein; Estrogen receptors; Estrogens; Gastrin; Gastrin-releasing peptide; Infiltration; Informed consent; Intravenous administration; Invasiveness; Lesions; Lungs; Lymph nodes; Mammography; Metastases; Metastasis; Nodes; Patients; Peptides; Positron emission; Radioactive tracers; Screening; Surgery; Tomography; Tumors
• ISSN: 0161-5505; 1535-5667

Objectives: This study was designed to assess a novel gastrin releasing peptide receptor (GRPR) and integrin αvβ3 dual targeting PET/CT using 68Ga-BBN-RGD in patients with breast cancer and metastasis, and to evaluate the correlation between imaging quantification and immunohistochemical result of GRPR and integrin αvβ3 expression within primary and metastatic breast cancer lesions. Methods: A macrocyclic chelator, 1,4,7-triazacyclononane-N,N’,N”-triacetic acid (NOTA) conjugated BBN-RGD was synthesized and labeled with 68Ga. With ethics committee approval and written informed consent, 22 patients (F, age range 29-62 y, mean age 52.5±9.3 y) were recruited either with suspected breast cancer on screening mammography (n=16) or underwent breast cancer radical mastectomy (n=6). All the 22 patients underwent PET/CT at 30-45 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of 68Ga-BBN-RGD. 11 of 22 patients also accepted 68Ga-BBN PET/CT within 2 weeks for a case-by-case comparison. All the 16 patients with highly suspicious breast lesions on screening mammography underwent surgery breast cancer radical mastectomy within one week after 68Ga-BBN-RGD PET/CT. For each of the 6 postoperative patients, at least one part of tissue biopsy was performed. A final diagnosis was made based on the histopathologic examination of surgical excision or biopsy. In total, 37 specimens from primary tumor and metastases were stained with GRPR, integrin αvβ3, estrogen receptor (ER), HER-2 and Ki-67 to correlate with 68Ga-BBN-RGD PET. Results: Both the primary cancer and metastases showed positive 68Ga-BBN-RGD accumulation. A total of 24 breast lesions were detected with 68Ga-BBN-RGD PET/CT in the 14 breast cancer patients including 2 intraductal carcinomas, 3 invasive ductal carcinomas, 6 intraductal carcinomas with infiltration, 2 invasive lobular carcinomas, and 1 metaplastic breast carcinoma with sizes ranging from 0.4 to 2.7 cm (mean, 1.6 ± 0.9 cm) and SUVmax from 1.7 to 8.5 (mean, 3.84 ± 2.18). A total of 12 regions recognized as having axillary metastatic lymph nodes and sized from 0.3 to 1.7 cm (mean, 0.9 ± 0.4 cm) were detected with 68Ga-BBN-RGD PET/CT in 4 breast cancer patients. The T/B ratios of 68Ga-BBN-RGD accumulation were 2.10 to 9.44 in primary cancer and 1.10 to 3.71 in axillary lymph node metastasis, 3.80 to 10.7 in distant lymph nodes, 2.70 to 5.35 in lung metastasis and 3.17 to 22.8 in bone metastasis, respectively. With the 11 patients underwent two PET scans, 68Ga-BBN-RGD PET/CT showed better primary tumor detection with an overall SUVmax of 3.84 ± 2.18, which was significantly higher that of 68Ga-BBN PET/CT (2.31 ± 0.72, P < 0.05). 68Ga-BBN-RGD PET/CT also showed higher SUVmax in bone metastases than 68Ga-BBN PET/CT (5.50 ± 2.43 vs. 2.17 ± 0.57, P < 0.05). For primary lesions, the SUVmax from 68Ga-BBN-RGD PET in ER positive group was higher than that in ER negative group (P < 0.01). Among the 37 pathologically confirmed primary tumors and metastases, GRPR expression was absent in 2 cases (5.4%), weak in 2 cases (5.4%), moderate in 25 cases (67.6%) and strong in 8 cases (21.6%). A moderate but significant correlation between SUVmean quantified from 68Ga-BBN-RGD PET and GRPR expression was identified (r2 = 0.4791, P < 0.0001). Integrin αvβ3 expression with different extent was also found in 23 out of 37 samples. There was a significant correlation between 68Ga-BBN-RGD SUVmean and αvβ3 expression (r2 = 0.3664, P < 0.001). Conclusion: This study demonstrated significant uptake of a new type of dual integrin αvβ3 and GRPR targeting radiotracer in both the primary lesion and the metastases of breast cancer. 68Ga-BBN-RGD PET/CT may be of great value in discerning both primary breast cancers, axillary lymph nodes metastasis and distant metastases, which indicates the efficacy of 68Ga-BBN-RGD PET/CT in breast cancer diagnosis, staging and therapy planning for the patients.