The Balance Between the Therapeutic Efficacy and Safety of [<superscript>177</superscript>Lu]Lu-NeoB in a Preclinical Prostate Cancer Model.
In: Molecular Imaging & Biology, Jg. 26 (2024-02-01), Heft 1, S. 114-123
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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The Balance Between the Therapeutic Efficacy and Safety of [<superscript>177</superscript>Lu]Lu-NeoB in a Preclinical Prostate Cancer Model.
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Autor/in / Beteiligte Person: | Verhoeven, Marjolein ; Haeck, Joost ; de Blois, Erik ; Orlandi, Francesca ; Barbato, Donato ; Tedesco, Mattia ; Konijnenberg, Mark ; Dalm, Simone U. |
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Zeitschrift: | Molecular Imaging & Biology, Jg. 26 (2024-02-01), Heft 1, S. 114-123 |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 1536-1632 (print) |
DOI: | 10.1007/s11307-023-01851-4 |
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