Development of a Novel HER2-Targeted Peptide Probe for Dual-Modal Imaging of Tumors

Abstract

Human epidermal growth factor receptor 2 (HER2) may serve as a valid target for diagnosis of cancer. The probes with capability for near-infrared window one region II (NIR-II) and positron emission tomography (PET) dual-modal imaging are highly desired for HER2-positive tumor detection. Herein, three HER2-targeted peptides were designed and further modified with indocyanine green (ICG) and 2,2′,2″,2″-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)­tetraacetic acid (DOTA), which were used for NIR-II imaging and complexation with 68Ga for PET. Among the resulted probes (DOTA-ZC01-ICG, DOTA-KSP-ICG, and DOTA-ZC02-ICG), NIR-II imaging revealed that DOTA-ZC02-ICG had the best tumor imaging performance in SKOV3 tumor-bearing mice. The highest T/N ratio (5.4) was achieved at 4 h post-injection. Furthermore, DOTA-ZC02-ICG was radiolabeled with 68Ga to generate [68Ga]-DOTA-ZC02-ICG for PET, and it clearly delineated at 0.5, 1, and 2 h post-injection. The tumor uptake reached 1.9 %ID/g at 0.5 h, and the tumor uptakes were significantly inhibited in the blocking study (p < 0.05). Overall, it provides a promising technique for tumor dual-modal imaging and a new molecular scaffold for developing HER2-targeted theranostic agents.

Multifunctional Probe Based on “Chemical Antibody–Aptamer” for Noninvasive Detection of PD-L1 Expression in Cancer

“…Fortunately, PET imaging possessed the advantages of high sensitivity and deep tissue penetration, which can complement NIRF imaging well. Therefore, by integrating the advantages of PET and NIRF imaging techniques, the dual-modality PET/NIRF imaging can accurately locate superficial and deep tumors, quantitatively detect the distribution of diseases, and precisely distinguish the boundary between tumor and adjacent normal tissues during the surgical resection. − …”

“…Positron emission tomography (PET) has been also used widely in the diagnosis, staging, and therapeutic evaluation of tumors owing to its remarkable advantages, such as high sensitivity, high specificity, deep tissue penetration, whole-body imaging, and low tracer dose. , Although PET imaging can accurately locate deep tumors and provide a whole-body image, it is difficult to clearly distinguish the tumor edge from normal tissues. Compared with the single-mode molecular imaging, dual-modality imaging integrates and highlights the common advantages of different imaging modes and can provide comprehensive molecular, metabolic, and anatomical information on diseases at the same time. , Therefore, by integrating the advantages of PET and NIRF imaging techniques, the dual-modality PET/NIRF imaging can accurately locate superficial and deep tumors, quantitatively evaluate the whole distribution of diseased tissues, and precisely distinguish the boundary between tumor and adjacent normal tissues during the surgical resection. − Hence, PET/NIRF dual-modality imaging plays an increasingly important role in the diagnosis and therapy of tumors.…”

Near-infrared dye IRDye800CW-NHS coupled to Trastuzumab for near-infrared II fluorescence imaging in tumor xenograft models of HER-2-positive breast cancer

“…18 However, ICG lacks specificity for tumors and has the disadvantage of being unstable in aqueous solution and prone to form H-dimer. 18–21 It has been reported that ICG-NHS based on ICG modification has the ability to couple with biomolecules, which is expected to be useful for targeting tumors, but the disadvantages that ICG-NHS is unstable in aqueous solution and prone to form H-dimer still exist. 22,23 The recently reported IRDye800CW is both biocompatible and easy to modify, the modified IRDye800CW can be directly reacted with biomolecules.…”

“…28,29 HER-2 gene amplification and protein overexpression are associated with aggressive clinical behaviors and poor prognosis of breast cancer. 21 The construction of fluorescent probes by combining Trastuzumab with fluorescent dyes in the NIR-II can strengthen the specificity of fluorescent dyes for breast cancer and enable accurate intraoperative diagnosis of breast cancer.…”

β-Galactosidase-Activated and Red Light-Induced RNA Modification Strategy for Prolonged NIR Fluorescence/PET Bimodality Imaging

“…Fortunately, near-infrared (NIR) fluorescence (FL) imaging has extensive application prospects in clinical practice for real-time visualization of tumors and guiding tumor resection due to its short image acquisition time and real-time generation of high sensitivity images. − However, the limited tissue penetration largely impedes its application to noninvasively detect tumor-associated biomarkers at deep tumors. It is reasonable to believe that the combination of NIR FL and PET can provide complementary signals for preoperative and intraoperative imaging of tumor site. − At present, several NIR FL/PET dual-modality probes, including small molecules, − polymers, − inorganic nanomaterials, − etc., , have been developed to offer precise signals for tumor imaging. However, most probes display “always-on” NIR FL and PET signals, which may result in a high whole-body signal and thus a reduced tumor/background ratio (TBR).…”