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

Müller, Cristina; Reber, Josefine; Haller, Stephanie; Dorrer, Holger; Bernhardt, Peter; Zhernosekov, Konstantin; Türler, Andreas; Schibli, Roger (2014). Direct in vitro and in vivo comparison of 161Tb and 177Lu using a tumour-targeting folate conjugate. European journal of nuclear medicine and molecular imaging, 41(3), pp. 476-485. Springer 10.1007/s00259-013-2563-z

[img] Text
art%3A10.1007%2Fs00259-013-2563-z.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (572kB) | Request a copy

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry
10 Strategic Research Centers > Albert Einstein Center for Fundamental Physics (AEC)
08 Faculty of Science > Physics Institute > Laboratory for High Energy Physics (LHEP)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Humangenetik

UniBE Contributor:

Reber, Josefine; Türler, Andreas and Schibli, Roger

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
500 Science > 530 Physics

ISSN:

1619-7070

Publisher:

Springer

Language:

English

Submitter:

Franziska Bornhauser-Rufer

Date Deposited:

18 Mar 2015 14:27

Last Modified:

24 Aug 2015 14:25

Publisher DOI:

10.1007/s00259-013-2563-z

BORIS DOI:

10.7892/boris.65204

URI:

https://boris.unibe.ch/id/eprint/65204

Actions (login required)

Edit item Edit item
Provide Feedback