99mTc-labeled iRGD for single-positron emission computed tomography imaging of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with a high mortality rate. One of the main reasons for this poor prognosis is the failure of a specific diagnosis. As a tumor-homing and penetrating peptide, iRGD has not only the properties of binding to neuropilin-1 and integrin αvβ3 but also internalizing into TNBC cells. In this study, we designed and prepared 99mTc-labeled iRGD (99mTc-HYNIC-iRGD) as a single-positron emission computed tomography (SPECT) imaging probe and investigated its feasibility for the targeted diagnosis of TNBC. The results showed that the iRGD peptide had acceptable biocompatibility within the studied concentration range and could specifically bind to TNBC cells in vitro. The 99mTc-HYNIC-iRGD was readily prepared with high radiochemical purity and stability. SPECT imaging of 99mTc-HYNIC-iRGD in a TNBC tumor-bearing mouse model showed obvious tumor accumulation with rapid blood clearance and favorable biodistribution. Our findings indicate that this active-targeted strategy has great potential to be developed as a novel tool for TNBC imaging.

Recent advances in the tumor‐penetrating peptide internalizing RGD for cancer treatment and diagnosis

“…Wang et al, 2016), photosensitizers (Yan et al, 2016;H. Zhang et al, 2022), nanoimaging probes (Yu et al, 2022), and so on.…”

“…These nanoparticles can link with iRGD through the maleimide‐thiol reaction (Huang et al, 2021), acrylamide‐addition reaction (Shen et al, 2014), and carboxyl‐amine amidation reaction (X. Li et al, 2016). Nanoparticles are often loaded with a variety of chemicals, including chemotherapeutic drugs (Dai et al, 2015; Jin et al, 2016; Song et al, 2012), nucleic acid molecules (Guan et al, 2021; Lo et al, 2018), small‐molecule inhibitors (J. Wang et al, 2016), photosensitizers (Yan et al, 2016; H. Zhang et al, 2022), nanoimaging probes (Yu et al, 2022), and so on. The nucleotide sequence of iRGD is linked to the nucleotide sequence of a protein or peptide via a peptide bond and expressed by an expression system to produce a recombinant antibody (Sha, Li, et al, 2015; Sha, Zou, et al, 2015) or recombinant protein (Lao et al, 2013, 2015; Yang, Yang, et al, 2019), or it can be coupled to a short peptide through a total chemical synthesis (Qifan et al, 2016). iRGD is linked to the membrane of biological cells, such as T cells (Ding et al, 2019) or red blood cells (RBCs) (C. Zhou et al, 2022), for treatment. The sequence of iRGD was inserted into the adenoviral vector and expressed on the surface of the adenovirus, conferring vector targeting (Al‐Zaher et al, 2018; Puig‐Saus et al, 2014).…”

“…These nanoparticles can link with iRGD through the maleimide‐thiol reaction (Huang et al, 2021), acrylamide‐addition reaction (Shen et al, 2014), and carboxyl‐amine amidation reaction (X. Li et al, 2016). Nanoparticles are often loaded with a variety of chemicals, including chemotherapeutic drugs (Dai et al, 2015; Jin et al, 2016; Song et al, 2012), nucleic acid molecules (Guan et al, 2021; Lo et al, 2018), small‐molecule inhibitors (J. Wang et al, 2016), photosensitizers (Yan et al, 2016; H. Zhang et al, 2022), nanoimaging probes (Yu et al, 2022), and so on.…”

“…X. Liu, Braun, et al (2017) integrated iRGD with an etched quantum dot system as a venous probe to detect tumors, selectively reducing the background signal and maintaining the tumor signal in vivo, thus improving the probe's selectivity, especially for connective tissue proliferative tumors. Yu et al (2022) designed 99mTc‐labeled iRGD (99mTc‐HYNIC‐iRGD) as an imaging probe for SPECT. In a tumor‐bearing mouse model of TNBC, 99mTc‐HYNIC‐iRGD SPECT imaging showed significant tumor accumulation, rapid blood clearance, and good biodistribution.…”

Recent Progress of Multifunctional Molecular Probes for Triple-Negative Breast Cancer Theranostics

“…Based on the fact that integrins and NRP-1 are highly expressed in TNBC, the iRGD peptide, functioning as a tumor-homing and penetrating peptide, exhibits properties of binding to neurociliin-1 and integrin αvβ3, along with being internalized into TNBC cells. The use of radionuclides to label the iRGD peptide enables the in vivo imaging of TNBC [ 28 ]. However, peptides also have some shortcomings such as being unstable and easily decomposed in vivo and having a short half-life [ 29 ], Further modifications may be needed to improve their functions.…”