Details

Autor(en) / Beteiligte

• Ruigrok, Eline A. M.
• Verhoeven, Marjolein
• Konijnenberg, Mark W.
• de Blois, Erik
• de Ridder, Corrina M. A.
• Stuurman, Debra C.
• Bertarione, Luisa
• Rolfo, Katia
• de Jong, Marion
• Dalm, Simone U.

Titel

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

Ist Teil von

• European journal of nuclear medicine and molecular imaging, 2022-11, Vol.49 (13), p.4440-4451

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2022

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• Purpose The radiolabeled gastrin-releasing peptide receptor (GRPR)-targeting antagonist NeoB is a promising radioligand for imaging and therapy of GRPR-expressing malignancies. In the current study, we aimed to discover the target organs of toxicity and the radiotoxic effects to these organs, when repeated dosages of [ 177 Lu]Lu-NeoB are administered to healthy female and male mice. Methods Animals received either 3 injections, with a 7-day interval, of vehicle (control group 1), 1200 pmol [ 175 Lu]Lu-NeoB (control group 2) or 40 MBq/400 pmol, 80 MBq/800 pmol, and 120 MBq/1200 pmol [ 177 Lu]Lu-NeoB (treatment groups 1, 2, and 3, respectively). At week 5, 19, and 43 after the first injection acute, early, and late organ toxicity, respectively, was determined. For this, histopathological and blood analyses were performed. To correlate the observed toxicity to absorbed dose, we also performed extensive biodistribution and dosimetry studies. Results The biodistribution study showed the highest absorbed doses in GRPR-expressing pancreas, the liver, and the kidneys (the main organs of excretion). Both control groups and almost all animals of treatment group 1 did not show any treatment-related toxicological effects. Despite the high absorbed doses, no clear microscopic signs of toxicity were found in the pancreas and the liver. Histological analysis indicated kidney damage in the form of hydronephrosis and nephropathy in treatment groups 2 and 3 that were sacrificed at the early and late time point. In the same groups, increased blood urea nitrogen levels were found. Conclusion In general, repeated administration of [ 177 Lu]Lu-NeoB was tolerated. The most significant radiotoxic effects were found in the kidneys, similar to other clinically applied radioligands. The results of this study underline the potential of [ 177 Lu]Lu-NeoB as a promising option for clinical therapy.