Preclinical assessment of Alzheimer's disease using novel designed 99mTc‐labeled RGD‐based pro‐apoptotic cyclic peptide as a promising SPECT agent

Abstract

The increased prevalence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and glioma results in increased risks to abolish the healthy life. This is because of inducing alternation causes into the intracellular compartment as well as noncell compartments. Therefore, herein, a simple and facile radiosynthesis strategy was employed for the development of a novel 99mTc (t1/2 = 6 h, Er = 140 keV) labeled diethylenetriamine pentaacetic acid (DTPA) conjugated cyclic heptapeptide (99mTc‐DTPA‐c[RGDKLAK]; cPT). The radiotracer was characterized using various analytical techniques to evaluate the identity, radiolabeling, biocompatibility, in vitro stability, and amenability for preclinical use. The biological specificity and efficacy of the radiolabeled cyclic peptide analog were confirmed by in vivo biodistribution and single‐photon emission computed tomography (SPECT) studies in Alzheimer disease (AD)‐induced animal models. The results demonstrated that 99mTc(CO)3‐DTPA‐cPT showed high radioactivity concentration at the site of αvβ3, α5β1‐integrins expressing brain regions while decreasing radioactivity levels in kidneys and increasing urinary bladder over the period of 3 h suggested the renal clearance route of the radiotracer. The diagnostic outcomes obtained from planar SPECT study are consistent with that of the biodistribution study with a target‐to‐nontarget ratio (T/NT = 28.47 ± 2.53) at 3‐h postinjection. The results are surprisingly supportive to our hypothesis that the small cyclic peptide‐based radiotracer is well‐oriented towards targeted drug delivery and envisaged that our proposed radiotracer 99mTc(CO)3‐DTPA‐cPT has potential diagnostic applications for Alzheimer's disease as a novel SPECT agent.