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Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer

Artikel i vetenskaplig tidskrift
Författare C. Muller
C. A. Umbricht
N. Gracheva
V. J. Tschan
G. Pellegrini
Peter Bernhardt
J. R. Zeevaart
U. Koster
R. Schibli
N. P. van der Meulen
Publicerad i European Journal of Nuclear Medicine and Molecular Imaging
Volym 46
Nummer/häfte 9
Sidor 1919-1930
ISSN 1619-7070
Publiceringsår 2019
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Sidor 1919-1930
Språk en
Länkar dx.doi.org/10.1007/s00259-019-04345...
Ämnesord Tb-161, Auger electrons, Prostate cancer, PSMA ligands, Radioligand therapy, membrane antigen-expression, radioligand therapy, lu-177, ligands, dosimetry, diagnosis, toxicity, in-111, assay, pet, Radiology, Nuclear Medicine & Medical Imaging
Ämneskategorier Fysik

Sammanfattning

PurposeThe prostate-specific membrane antigen (PSMA) has emerged as an interesting target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). The aim of this study was to investigate Tb-161 (T-1/2=6.89days; E beta(?)(av)=154keV) in combination with PSMA-617 as a potentially more effective therapeutic alternative to Lu-177-PSMA-617, due to the abundant co-emission of conversion and Auger electrons, resulting in an improved absorbed dose profile.Methods(161)Tb was used for the radiolabeling of PSMA-617 at high specific activities up to 100MBq/nmol. Tb-161-PSMA-617 was tested in vitro and in tumor-bearing mice to confirm equal properties, as previously determined for Lu-177-PSMA-617. The effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 on cell viability (MTT assay) and survival (clonogenic assay) were compared in vitro using PSMA-positive PC-3 PIP tumor cells. Tb-161-PSMA-617 was further investigated in therapy studies using PC-3 PIP tumor-bearing mice.Results(161)Tb-PSMA-617 and Lu-177-PSMA-617 displayed equal in-vitro properties and tissue distribution profiles in tumor-bearing mice. The viability and survival of PC-3 PIP tumor cells were more reduced when exposed to Tb-161-PSMA-617 as compared to the effect obtained with the same activities of Lu-177-PSMA-617 over the whole investigated concentration range. Treatment of mice with Tb-161-PSMA-617 (5.0MBq/mouse and 10MBq/mouse, respectively) resulted in an activity-dependent increase of the median survival (36 vs 65days) compared to untreated control animals (19days). Therapy studies to compare the effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 indicated the anticipated superiority of Tb-161 over Lu-177.Conclusion(161)Tb-PSMA-617 showed superior in-vitro and in-vivo results as compared to Lu-177-PSMA-617, confirming theoretical dose calculations that indicate an additive therapeutic effect of conversion and Auger electrons in the case of Tb-161. These data warrant more preclinical research for in-depth investigations of the proposed concept, and present a basis for future clinical translation of Tb-161-PSMA-617 for the treatment of mCRPC.

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