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- Title
The Balance Between the Therapeutic Efficacy and Safety of [<sup>177</sup>Lu]Lu-NeoB in a Preclinical Prostate Cancer Model.
- Authors
Verhoeven, Marjolein; Haeck, Joost; de Blois, Erik; Orlandi, Francesca; Barbato, Donato; Tedesco, Mattia; Konijnenberg, Mark; Dalm, Simone U.
- Abstract
Purpose: Radiolabeled NeoB is a promising gastrin-releasing peptide receptor (GRPR)–targeting radiopharmaceutical for theranostics of GRPR-expressing malignancies, e.g., prostate cancer (PCa). The aim of this study was to evaluate the effect of different doses of [177Lu]Lu-NeoB on the balance between therapeutic efficacy and safety in a preclinical PCa model. Procedures: To determine the efficacy of [177Lu]Lu-NeoB, PC-3 xenografted mice received 3 sham injections (control group) or 3 injections of 30 MBq/300 pmol, 40 MBq/400 pmol, or 60 MBq/600 pmol [177Lu]Lu-NeoB (groups 1, 2, and 3, respectively) 1 week apart. To quantify tumor uptake, single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was performed 4 h after the first, second, and third injection on a separate group of animals. For safety evaluations, pancreatic and renal tissues of non-tumor-bearing mice treated with the abovementioned [177Lu]Lu-NeoB doses were evaluated 12 and 24 weeks post-treatment. Results: Treatment of PC-3 tumors with all three studied [177Lu]Lu-NeoB doses was effective. Median survival times were significantly (p < 0.0001) improved for treatment groups 1, 2, and 3 versus the control group (82 days, 89 days, 99 days versus 19 days, respectively). However, no significant differences were observed between treatment groups. Quantification of SPECT/CT images showed minimal differences in the average absolute radioactivity uptake, especially after the third injection. Histopathological analysis revealed no clear signs of treatment-related pancreatic toxicity. For the kidneys, atrophy and fibrosis were observed for one animal from group 1 and a chronic inflammatory response was observed for both animals from group 3 at 24 weeks post-treatment. Conclusions: Treatment with [177Lu]Lu-NeoB is effective in a preclinical PCa model. Adjusting the administered dose could positively impact the risk-benefit balance as a higher dose might not lead to an increased therapeutic effect, but it may lead to an increase in toxicological effects in healthy organs such as the kidneys.
- Subjects
SINGLE-photon emission computed tomography; TREATMENT effectiveness; PROSTATE cancer; PEPTIDE receptors; COMPUTED tomography; LUTETIUM compounds
- Publication
Molecular Imaging & Biology, 2024, Vol 26, Issue 1, p114
- ISSN
1536-1632
- Publication type
Article
- DOI
10.1007/s11307-023-01851-4