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Therapeutic Potential of Sc-47 in Comparison to Lu-177 and Y-90: Preclinical Investigations

Journal article
Authors K. Siwowska
P. Guzik
K. A. Domnanich
J. M. M. Rodriguez
Peter Bernhardt
B. Ponsard
R. Hasler
F. Borgna
R. Schibli
U. Koster
N. P. van der Meulen
C. Muller
Published in Pharmaceutics
Volume 11
Issue 8
Publication year 2019
Published at Institute of Clinical Sciences, Department of Radiation Physics
Language en
Links dx.doi.org/10.3390/pharmaceutics110...
Keywords Sc-47, Lu-177, Y-90, radionuclide therapy, SPECT, folate receptor, DOTA-folate, IGROV-1 tumor, receptor radionuclide therapy, tumor-therapy, in-vitro, vivo, y-90-dotatoc, toxicity, growth, beta, Pharmacology & Pharmacy
Subject categories Radiology, Nuclear Medicine and Medical Imaging

Abstract

Targeted radionuclide therapy with Lu-177- and Y-90-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. Sc-47 is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy beta(-)particles. In this study, Sc-47 was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of Lu-17-folate and Y-90-folate, respectively. In vitro, Sc-47-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to Lu-177-folate, but Y-90-folate was more potent at equal activities due to the higher energy of emitted beta(-)particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (similar to 21 Gy) when treated with Sc-47-folate (12.5 MBq), Lu-177-folate (10 MBq), and Y-90-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, Sc-47 is likely to be comparable to Lu-177 when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with Sc-44 or Sc-43 as a diagnostic match, enabling the realization of radiotheragnostics in future.

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