PT  - JOURNAL ARTICLE
AU  - Zhang, Mingru
AU  - Jacobson, Orit
AU  - Kiesewetter, Dale
AU  - Ma, Ying
AU  - Lang, Lixin
AU  - Wang, Zhantong
AU  - Niu, Gang
AU  - Wang, Jing
AU  - Chen, Xiaoyuan
TI  - <strong>Improving the theranostic potential of HER2 Affibody by reducing the renal radioactivity through brush border membrane enzyme-mediated degradation</strong>
DP  - 2020 May 01
TA  - Journal of Nuclear Medicine
PG  - 1221--1221
VI  - 61
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/61/supplement_1/1221.short
4100  - http://jnm.snmjournals.org/content/61/supplement_1/1221.full
SO  - J Nucl Med2020 May 01; 61
AB  - 1221Purpose: Human epidermal growth factor receptor 2 (HER2) is overexpressed in various types of tumors, & radiolabeled HER2 Affibody is believed to be an attractive tool for HER2 targeted theranostics. However, its wide application is limited by the lack of high & persistent radioactivity accumulation in kidneys. In this study, we intend to reduce the renal accumulation of radiolabeled HER2 Affibody through degradation mediated by brush border membrane enzymes. Materials and Methods: A new HER2 Affibody ligand NOTA-MVK-HER2 Affibody containing Met-Val-Lys (MVK) linker between the peptide and 1,4,7-triazacyclononane-1,4,7 -triacetic acid (NOTA) chelator was synthesized and labeled with 68Ga. The in vitro PBS & mouse serum stability of the tracer were evaluated. The microPET images were acquired in SKOV-3 tumor model at different time points, the radioactivity uptake of 68Ga-NOTA-MVK-HER2 Affibody in tumor & kidneys were determined & compared with the control radiotracer without MVK linker. Results: 68Ga-NOTA-MVK-HER2 Affibody was stable in PBS and mouse serum. MicroPET images showed that the tumor uptake of 68Ga-NOTA-MVK-HER2 Affibody was comparable to that of the control, while the kidney uptake was significantly reduced. As a result, more favorable tumor to kidney ratios were achieved. Conclusions: In this study, a novel HER2 Affibody analogue, NOTA-MVK-HER2 Affibody, was successfully synthesized & labeled with 68Ga. As the high & consistent renal radioactivity accumulation could be significantly reduced, NOTA-MVK-HER2 Affibody shows great potential in the diagnosis & radiotherapy for HER2 positive tumors.