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European Journal of Nuclear Medicine and Molecular Imaging

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01.06.2009 | Original Article

Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy

verfasst von: Cristina Müller, Thomas L. Mindt, Marion de Jong, Roger Schibli

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2009

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Abstract

Purpose

Folate-based radiopharmaceuticals have the potential to be used for imaging and therapy of tumours positive for the folate receptor (FR). We describe the in vitro and in vivo evaluation of a DOTA–folate conjugate.

Methods

Radiolabelling of the DOTA-folate was carried out via standard procedures using ¹¹¹InCl₃ and ¹⁷⁷LuCl₃, respectively. The distribution coefficient (log D) was determined in octanol/PBS (pH 7.4). Tissue distribution was investigated in nude mice bearing KB tumour xenografts at different time points after administration of ¹¹¹In-DOTA-folate (radiofolate 1) or ¹⁷⁷Lu-DOTA-folate (radiofolate 2) (1 MBq, 1 nmol per mouse). Pemetrexed (PMX, 400 μg) was injected 1 h prior to the radiofolate in order to reduce renal uptake. Images were acquired with a SPECT/CT camera 24 h after injection of the radiofolate (40–50 MBq, 3 nmol per mouse).

Results

The hydrophilic character of the DOTA-folate was represented by a low log D value (radiofolate 1 −4.21±0.11). In vivo, maximal tumour uptake was found 4 h after injection (radiofolate 1 5.80±0.55% ID/g; radiofolate 2 7.51±1.25% ID/g). In FR-positive kidneys there was considerable accumulation of the radiofolates (radiofolate 1 55.88±3.91% ID/g; radiofolate 2 57.22±11.05% ID/g; 4 h after injection). However, renal uptake was reduced by preinjection of PMX (radiofolate 1 9.52±1.07% ID/g; radiofolate 2 13.43±0.54% ID/g; 4 h after injection) whereas the tumour uptake was retained (radiofolate 1 6.32±0.41% ID/g; radiofolate 2 8.99±0.43% ID/g; 4 h after injection). SPECT/CT images clearly confirmed favourable tissue distribution of the novel radiofolates and the positive effect of PMX.

Conclusion

The preliminary requirements for the therapeutic use of the novel DOTA-folate are met by its favourable tissue distribution that can be ascribed to its hydrophilic properties and combined administration with PMX.

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Titel: Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy
verfasst von: Cristina Müller
Thomas L. Mindt
Marion de Jong
Roger Schibli
Publikationsdatum: 01.06.2009
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-008-1058-9

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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