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European Journal of Nuclear Medicine and Molecular Imaging

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01-03-2014 | Original Article

Direct in vitro and in vivo comparison of ¹⁶¹Tb and ¹⁷⁷Lu using a tumour-targeting folate conjugate

Authors: Cristina Müller, Josefine Reber, Stephanie Haller, Holger Dorrer, Peter Bernhardt, Konstantin Zhernosekov, Andreas Türler, Roger Schibli

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2014

Abstract

Purpose

The radiolanthanide ¹⁶¹Tb (T _1/2 = 6.90 days, Eβ⁻ _av = 154 keV) was recently proposed as a potential alternative to ¹⁷⁷Lu (T _1/2 = 6.71 days, Eβ⁻ _av = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare ¹⁶¹Tb and ¹⁷⁷Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09).

Methods

¹⁶¹Tb-cm09 and ¹⁷⁷Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo ¹⁶¹Tb-cm09 and ¹⁷⁷Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using ^99mTc-dimercaptosuccinic acid (DMSA).

Results

To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for ¹⁶¹Tb-cm09 (IC₅₀ ~0.014 MBq/ml and ~2.53 MBq/ml) compared to ¹⁷⁷Lu-cm09 (IC₅₀ ~0.063 MBq/ml and ~4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies ¹⁶¹Tb-cm09 reduced tumour growth more efficiently than ¹⁷⁷Lu-cm09. These findings were in line with the higher absorbed tumour dose for ¹⁶¹Tb-cm09 (3.3 Gy/MBq) compared to ¹⁷⁷Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates.

Conclusion

Compared to ¹⁷⁷Lu-cm09 we demonstrated equal imaging features for ¹⁶¹Tb-cm09 but an increased therapeutic efficacy for ¹⁶¹Tb-cm09 in both tumour cell lines in vitro and in vivo. Further preclinical studies using other tumour-targeting radioconjugates are clearly necessary to draw final conclusions about the future clinical perspectives of ¹⁶¹Tb.

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Title: Direct in vitro and in vivo comparison of 161Tb and 177Lu using a tumour-targeting folate conjugate
Authors: Cristina Müller
Josefine Reber
Stephanie Haller
Holger Dorrer
Peter Bernhardt
Konstantin Zhernosekov
Andreas Türler
Roger Schibli
Publication date: 01-03-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-013-2563-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Direct in vitro and in vivo comparison of ¹⁶¹Tb and ¹⁷⁷Lu using a tumour-targeting folate conjugate

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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