Evaluation of Actinium-225 Labeled Minigastrin Analogue [225 Ac]Ac-DOTA-PP-F11N for Targeted Alpha Particle Therapy

Pharmaceutics
Yun QinMichal Grzmil

Abstract

The overexpression of cholecystokinin B receptor (CCKBR) in human cancers led to the development of radiolabeled minigastrin analogues for targeted radionuclide therapy, which aims to deliver cytotoxic radiation specifically to cancer cells. Alpha emitters (e.g., actinium-225) possess high potency in cancer cell-killing and hold promise for the treatment of malignant tumors. In these preclinical studies, we developed and evaluated CCKBR-targeted alpha particle therapy. The cellular uptake and cytotoxic effect of actinium-225 labeled and HPLC-purified minigastrin analogue [225Ac]Ac-PP-F11N were characterized in the human squamous cancer A431 cells transfected with CCKBR. Nude mice bearing A431/CCKBR tumors were used for biodistribution and therapy studies followed by histological analysis and SPECT/CT imaging. In vitro, [225Ac]Ac-PP-F11N showed CCKBR-specific and efficient internalization rate and potent cytotoxicity. The biodistribution studies of [225Ac]Ac-PP-F11N revealed CCKBR-specific uptake in tumors, whereas the therapeutic studies demonstrated dose-dependent inhibition of tumor growth and extended mean survival time, without apparent toxicity. The histological analysis of kidney and stomach indicated no severe adverse ef...Continue Reading

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Citations

Jul 3, 2021·Pharmaceutics·Romain EychenneJean-François Gestin

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Methods Mentioned

BETA
X-ray
xenograft

Clinical Trials Mentioned

NCT03246659
NCT02088645

Software Mentioned

GraphPad Prism
VivoQuant

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