99m Tc-Labeled D-Type PTP as a Plectin-Targeting Single-Photon Emission Computed Tomography Probe for Hepatocellular Carcinoma Imaging

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Plectin, a scaffolding protein overexpressed in tumor cells, plays a significant role in hepatocellular carcinoma (HCC) proliferation, invasion, and migration. However, the use of L-type peptides for targeting plectin is hindered by their limited stability and retention. We designed a D-type plectin-targeting peptide ( D PTP) and developed a novel single-photon emission computed tomography (SPECT) probe for HCC imaging. The D PTP targeting ability was evaluated in vitro using flow cytometry and ex vivo fluorescence imaging. 99m Tc radiolabeling was performed using tricine and ethylenediamine- N, N ′-diacetic acid (EDDA) as coligands after modification with 6-hydrazino nicotinamide (HYNIC) at the N termini of D PTP. The radiochemical purity (RCP), in vitro stability, and binding affinity of the prepared 99m Tc-HYNIC- D PTP were analyzed. Tumor uptake, metabolic stability, biodistribution, and pharmacokinetics of 99m Tc-HYNIC- D PTP were investigated and compared with those of 99m Tc-labeled L-type PTP ( 99m Tc-HYNIC-PTP) in HCC tumor-bearing mice. D PTP could be efficiently radiolabeled with 99m Tc using the HYNIC/tricine/EDDA system with a high RCP and good in vitro stability. Compared with the L-type PTP, D PTP exhibited improved targeting ability, and 99m Tc-HYNIC- D PTP displayed higher tumor uptake, better metabolic stability, longer blood circulation time, and lower kidney retention, resulting in superior imaging performance and biodistribution in vivo . 99m Tc-HYNIC- D PTP has great potential as a novel SPECT probe for diagnosing HCC.

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