Gold Nanoparticles Loaded With Lutetium‐177 Labeled DOTA‐TATE Exhibit Superior AR42J Cell Affinity and Extended Blood Circulation in AR42J Tumor Xenografts

ABSTRACT Lutetium‐177 ( 177 Lu) labeled DOTA‐3‐Tyr‐Octreotate (DOTA‐TATE) is a peptide‐based receptor‐mediated radionuclide therapy that has received FDA authorization for treatment of neuroendocrine tumors expressing somatostatin sstr2 receptors. The present study employs a synthetically modified gold nanoparticle (AuNP) preparation for effecting increased delivery of [ 177 Lu]Lu‐DOTA‐TATE at the targeted cancerous site. Two synthetic approaches, viz. pre‐labeling and post‐labeling , were followed to produce the [ 177 Lu]Lu‐DOTA‐TATE‐loaded AuNPs. The pre‐labeling approach estimated the peptide functionalization to an extent of ∼20%. TEM of DOTA‐TATE functionalized AuNPs yielded a particle size around 5.5 ± 2.2 nm. A theoretical estimate quantified the average number of TATE molecules per AuNP around 23. IC 50 determination of DOTA‐TATE functionalized AuNP using [ 177 Lu]Lu‐DOTA‐TATE as a standard in AR42J cell lines exhibited superior inhibition (0.62 nM) in comparison to free DOTA‐TATE peptide (4.84 nM). The radiolabeled AuNPs presented >80% specificity in AR42J cell lines. Biodistribution studies of radiolabeled AuNPs in AR42J tumor xenografts showed tumor uptake of 1.76 ± 1.08% ID/g at 2 h post‐injection (p.i.), which remained nearly constant over a period of 48 h. Unlike the standard [ 177 Lu]Lu‐DOTA‐TATE radiotracer, the NP elimination from the blood pool was slower; however, prolonged systemic circulation failed to enhance tumor accumulation over time.