Octreotide (Imagine Pharma)

Peptide receptor radionuclide therapy (PRRT) with proven targeting ability has emerged as a new paradigm for clinical tumor therapy. The selective binding of octreotide to somatostatin receptor 2 (SSTR2) renders the successful development of ¹⁷⁷Lu-DOTATATE for SSTR2-positive neuroendocrine tumor patients. Here, we find that naphthalene-containing octreotide radioligand (OCT(naph)) induces elevated tumor uptake and radionuclide therapy for SSTR2-positive tumor over DOTATATE. ¹⁷⁷Lu-OCT(naph) demonstrated high radiochemical purity and radiostability, and increased binding affinity to human serum albumin, which led to prolonged blood circulation time and a peak accumulation of 20.8 ± 3.2 %ID/g, 1.6-fold of that for ¹⁷⁷Lu-DOTATATE, in SSTR2⁺ HCT-116 tumor. A single injection of ¹⁷⁷Lu-OCT(naph) at 7.4 MBq while induced no apparent toxicity effectively suppressed tumor growth, significantly outperforming ¹⁷⁷Lu-DOTATATE. Overall, ¹⁷⁷Lu-OCT(naph) with optimized albumin binding appears as a potentially better radionuclide therapy for SSTR2-positive tumors.