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In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study.
Rottenburger, Christof; Hentschel, Michael; Fürstner, Markus; McDougall, Lisa; Kottoros, Danijela; Kaul, Felix; Mansi, Rosalba; Fani, Melpomeni; Vija, A Hans; Schibli, Roger; Geistlich, Susanne; Behe, Martin; Christ, Emanuel R; Wild, Damian.
Afiliação
  • Rottenburger C; Division of Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
  • Hentschel M; Division of Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
  • Fürstner M; Division of Medical Radiation Physics, Department of Radiation Oncology, Bern University Hospital, Bern, Switzerland.
  • McDougall L; Division of Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
  • Kottoros D; Division of Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
  • Kaul F; Division of Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
  • Mansi R; Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland.
  • Fani M; Division of Radiopharmaceutical Chemistry, University Hospital Basel, Basel, Switzerland.
  • Vija AH; Division of Radiopharmaceutical Chemistry, University Hospital Basel, Basel, Switzerland.
  • Schibli R; Molecular Imaging, Siemens Medical Solutions USA, Inc., Hoffman Estates, IL, USA.
  • Geistlich S; Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH, Zurich, Switzerland.
  • Behe M; Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, Villigen, Switzerland.
  • Christ ER; Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, Villigen, Switzerland.
  • Wild D; Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, Villigen, Switzerland.
EJNMMI Res ; 14(1): 37, 2024 Apr 06.
Article em En | MEDLINE | ID: mdl-38581480
ABSTRACT

BACKGROUND:

A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [177Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [177Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto® pretreatment in an open-label, randomized cross-over order. Entresto® was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated.

RESULTS:

Pretreatment with Entresto® showed no additional toxicity and increased the stability of [177Lu]Lu-PP-FF11N in blood significantly (p < 0.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto® pretreatment (0.74 vs. 0.28 Gy/GBq, P = 0.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto®.

CONCLUSIONS:

Premedication with Entresto® results in a relevant stabilization of [177Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs. Trial registration clinicaltrails.gov, NCT03647657. Registered 20 August 2018.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article