In Vivo Biodistribution and Efficacy Evaluation of NeoB, a Radiotracer Targeted to GRPR, in Mice Bearing Gastrointestinal Stromal Tumor

Abstract

NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein–coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice bearing GIST-882 tumors were employed. [177Lu]Lu-NeoB biodistribution was evaluated up to seven days by organ sampling (200 pmol/0.8 MBq, i.v.). For efficacy evaluation, mice received either saline, 400 pmol or 800 pmol of [177Lu]Lu-NeoB (37MBq, 1/w, 3 w, i.v.). SPECT/CT imaging was performed at 24 h, and tumor volume was determined up to 100 days. Elevated and specific [177Lu]Lu-NeoB uptake was found in the GIST tumor, as demonstrated by in vivo competition (19.1 ± 3.9 %ID/g vs. 0.3 ± 0.1 %ID/g at 4h). [177Lu]Lu-NeoB tumor retention (half-life of 40.2 h) resulted in elevated tumor-to-background ratios. Tumor volumes were significantly reduced in both treated groups (p < 0.01), even leading to complete tumor regression at the 400 pmol dose. [177Lu]Lu-NeoB exhibited excellent pharmacokinetics with elevated and prolonged tumor uptake and low uptake in non-target organs such as pancreas. The potential of this new theragnostic agent in different indications, including GIST, is under evaluation in the FIH [177Lu]Lu-NeoB clinical trial.

Safety of [177Lu]Lu-NeoB treatment: a preclinical study characterizing absorbed dose and acute, early, and late organ toxicity

“…Furthermore, no histopathological signs of continuous or severe pancreatic toxicity was observed. These findings are in agreement with the study by Montemagno et al (2021) who also reported no pancreatic alterations 100 days after mice bearing gastrointestinal stromal tumors were treated once weekly for 3 consecutive weeks with 37 MBq/400 pmol [ 177 Lu]Lu-NeoB [24].…”

Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer

“…The therapeutic dosing regimen can still be optimized by potentially determining the number of doses needed to achieve a prolonged therapeutic effect and/or determining the intervals between doses, as the shorter half-life of 67 Cu compared to 177 Lu may allow for shorter treatment intervals. For example, a recent paper on [ 177 Lu]Lu-NeoB in animal models has proposed a weekly dose of 37 MBq for 3 weeks, which resulted in tumor inhibition in gastrointestinal stromal tumors (GIST) xenograft model [35].…”

Personalized Targeted Therapeutic Strategies against Oral Squamous Cell Carcinoma. An Evidence-Based Review of Literature

“…78,79 recognized with increased GRPR, and emerging studies have investigated the possibility of targeted diagnosis and therapy using GRPR, such as in breast cancer, gastrointestinal cancer, colorectal cancer, and so on. [81][82][83] In OSCC, Lango et al have reported that GRPR expression was six times higher than that in normal tissues, and four times higher than that in adjacent normal epithelial tissues. 84 Furthermore, studies focusing on near-infrared fluorescent imaging of OSCC utilized GRPR targeting, and results showed that it's available in intraoperative surgical margin decision and metastatic lymph node detection.…”