[99mTc]Tc-Labeled Plectin-Targeting Peptide as a Novel SPECT Probe for Tumor Imaging

Abstract

Certain receptors are often overexpressed during tumor occurrence and development and closely correlate with carcinogenesis. Owing to its overexpression on the cell membrane and cytoplasm of various tumors, plectin, which is involved in tumor proliferation, migration, and invasion, has been viewed as a promising target for cancer imaging. Hence, plectin-targeting agents have great potential as imaging probes for tumor diagnosis. In this study, we developed a [99mTc]Tc-labeled plectin-targeted peptide (PTP) as a novel single-photon emission computed tomography (SPECT) probe for tumor imaging and investigated its pharmacokinetics, biodistribution, and targeting ability in several types of tumor-bearing mouse models. The PTP had good biocompatibility and targeting ability to tumor cells in vitro and could be readily labeled with [99mTc]Tc after modification with the bifunctional chelator 6-hydrazino nicotinamide (HYNIC). Furthermore, the prepared [99mTc]Tc-labeled PTP ([99mTc]Tc-HYNIC-PTP) showed high radiochemical purity and excellent stability in vitro. In addition, favorable biodistribution, fast blood clearance, and clear accumulation of [99mTc]Tc-HYNIC-PTP in several types of tumors were observed, with a good correlation between tumor uptake and plectin expression levels. These results indicate the potential of [99mTc]Tc-HYNIC-PTP as a novel SPECT probe for tumor imaging.

Preparation and bioevaluation of [99mTc]Tc-labeled A7R and DA7R for SPECT imaging of triple-negative breast cancer

“…The RCPs of [ 99m Tc]Tc-labeled peptides can be rapidly estimated using the TLC method reported in the literature. 37 As shown in Fig. 5C and F, after performing the reaction mixture by TLC plates using methanol containing 1% HCl as the mobile phase, single peaks of [ 99m Tc] Tc-HYNIC-A7R and [ 99m Tc]Tc-HYNIC-D A7R were observed with a retention factor of 0.5, whereas the retention factors of colloidal [ 99m Tc]Tc and unreacted Na[ 99m Tc]TcO 4 were 0 and 1, respectively.…”

“…[ 99m Tc]Tc-HYNIC-A7R and [ 99m Tc]Tc-HYNIC- D A7R were prepared as previously described. 37 Briefly, 50 μL of HYNIC-A7R or HYNIC- D A7R solution (1 mg mL −1 in water), 0.5 mL EDDA solution (20 mg mL −1 in 0.1 M NaOH), 0.5 mL tricine solution (40 mg mL −1 in 0.2 M PBS, pH = 6.0), 1 mL Na[ 99m Tc]TcO 4 solution (50 mCi mL −1 ), and 50 μL SnCl 2 solution (1 mg mL −1 in 0.1 M HCl) were mixed and incubated at 100 °C. After 15 min, the reaction solution was cooled to room temperature and characterized using radio-HPLC.…”

“…In our previous study, we reported a [ 99m Tc]Tc-labeled HYNIC-modified heptapeptide with high RCP and excellent stability, which exhibited favorable accumulation in several types of tumors. 37 Therefore, we used HYNIC to modify A7R and D A7R peptides, which were then readily labeled with [ 99m Tc]Tc using tricine and ethylenediamine-N,N 0diacetic acid (EDDA) as co-ligands according to the literature. 38 The prepared [ 99m Tc]Tc-HYNIC-A7R and [ 99m Tc]Tc-HYNIC-D A7R were characterized using radio-HPLC.…”

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

“…HYNIC-iRGD, HYNIC-iRGE, and HYNIC-CG 7 C were labeled with 99m Tc according to previously published procedures in the literature ( Bohn et al, 2013 ; Xu et al, 2017 ; Gong et al, 2022 ). In brief, a mixture of 50 μl HYNIC-modified peptide (1 mg/ml in water), 0.5 ml EDDA solution (20 mg/ml in 0.1 M NaOH), 0.5 ml tricine solution (40 mg/ml in 0.2 M PBS, pH = 6.0), 1 ml Na 99m TcO4 solution (50 mCi/ml), and 50 μl SnCl 2 solution (1 mg/ml in 0.1 M HCl) were heated at 100°C for 15 min.…”