Biodistribution of Novel 68Ga-Radiolabelled HER2 Aptamers in Mice

Abstract

Background: Two novel HER2 aptamers were recently selected with great potential for the in vitro diagnosis of HER2-positive cancer. The goal of this study was to examine the in vivo diagnostic potential of these HER2 aptamers.

Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach

“…After binding to targeted surface receptors, aptamers are internalised with their payloads to exert their effects [27,46,121]. Previous research with radiolabelled aptamers (summarised in Table 2) has demonstrated efficacy in recognising targets for molecular imaging, when conjugated with specific radioisotopes such as copper-64 ( 64 Cu), 18 F and 68 Ga [22,118,[122][123][124]. Thus, aptamers can be radiolabelled and functionalised with different radioisotopes using chelators or by applying strategies of radiolabelling antibodies and nanobodies to aptamers [22,118].…”

“…Gijs et al [124] developed two DNA aptamers to target the HER2 receptor using a whole-cell SELEX approach. The two aptamers, HeA2_1 and HeA2_3, demonstrated specific binding to HER2(+) cell lines (SKOV3 and SK-BR-3) and HER2(+) tumours when compared to the MDA-MB-231 cell line.…”

“…The two aptamers, HeA2_1 and HeA2_3, demonstrated specific binding to HER2(+) cell lines (SKOV3 and SK-BR-3) and HER2(+) tumours when compared to the MDA-MB-231 cell line. HeA2_3 demonstrated internalisation by SKOV3 (ovarian adenocarcinoma) by comparing the cellular localisation of the aptamer against that of the anti-HER2 antibody [124]. Internalisation of the aptamer was confirmed by local fluorescent intensity in the cytoplasm, unlike the anti-HER2 antibody localised at the cell-surface (characteristic localisation of HER2 receptors) [124].…”

“…HeA2_3 demonstrated internalisation by SKOV3 (ovarian adenocarcinoma) by comparing the cellular localisation of the aptamer against that of the anti-HER2 antibody [124]. Internalisation of the aptamer was confirmed by local fluorescent intensity in the cytoplasm, unlike the anti-HER2 antibody localised at the cell-surface (characteristic localisation of HER2 receptors) [124]. Interestingly, HeA2_1 and HeA2_3 also inhibited cell-proliferation of SKOV3 cells by 1.26-fold and 1.30-fold respectively, when compared to untreated cells and the negative control aptamer [124].…”

Radiolabeling of Nucleic Acid Aptamers for Highly Sensitive Disease-Specific Molecular Imaging

“…68 Ga 3+ creates insoluble Ga(OH) 3 (gallium hydroxide) complexes at pH between 3 and 7, owing to strong affinity for hydroxide anions [95]. Radiolabeling of conjugated HER 2 aptamer was performed using a lyophilized aptamer in a HEPES buffer and incubated for at least 5 min at room temperature (Figure 21) [96]. In 2015, Kang et al reported 68 Ga labeling of uMUC-1 (underglycosylated mucin-1, an early marker of tumor development) targeting an aptamer using a p–SCN–bn–NOTA chelating agent [97].…”