TY - JOUR
T1 - Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations
AU - Siwowska, Klaudia
AU - Guzik, Patrycja
AU - Domnanich, Katharina A.
AU - Monné Rodriguez, Josep M.
AU - Bernhardt, Peter
AU - Ponsard, Bernard
AU - Hasler, Roger
AU - Borgna, Francesca
AU - Schibli, Roger
AU - Köster, Ulli
AU - van der Meulen, Nicholas P.
AU - Müller, Cristina
N1 - Score=10
PY - 2019/8/20
Y1 - 2019/8/20
N2 - Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinicallyestablished treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy 蚠-particles. In this study, 47Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of 177Lu-folate and 90Y-folate, respectively. In vitro, 47Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to 177Lu-folate, but 90Y-folate was more potent at equal activities due to the higher energy of emitted 蚠-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5MBq), 177Lu-folate (10MBq), and 90Y-folate (5MBq), 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, 47Sc is likely to be comparable to 177Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with 44Sc or 43Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.
AB - Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinicallyestablished treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy 蚠-particles. In this study, 47Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of 177Lu-folate and 90Y-folate, respectively. In vitro, 47Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to 177Lu-folate, but 90Y-folate was more potent at equal activities due to the higher energy of emitted 蚠-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5MBq), 177Lu-folate (10MBq), and 90Y-folate (5MBq), 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, 47Sc is likely to be comparable to 177Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with 44Sc or 43Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.
KW - Radionucliede therapy
KW - SPECT
KW - folate receptor
KW - DOTA-folate
KW - IGROV-1 tumor xenografts
KW - preclinical therapy
KW - 177-Lu
KW - 47-Sc
KW - 90Y
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/35144998
U2 - 10.3390/pharmaceutics11080424
DO - 10.3390/pharmaceutics11080424
M3 - Article
SN - 1999-4923
VL - 11
SP - 1
EP - 13
JO - Pharmaceutics
JF - Pharmaceutics
IS - 8
ER -