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

Müller, Cristina ; Mindt, Thomas ; de Jong, Marion ; Schibli, Roger

In: European Journal of Nuclear Medicine and Molecular Imaging, 2009, vol. 36, no. 6, p. 938-946

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    Titre
    • Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy
    Auteur
    • Müller, Cristina. Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland
    • Mindt, Thomas. Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland
    • de Jong, Marion. Department of Nuclear Medicine, Erasmus MC, 3015 CE, Rotterdam, The Netherlands
    • Schibli, Roger. Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • European Journal of Nuclear Medicine and Molecular Imaging, 2009, vol. 36, no. 6, p. 938-946. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:318117
    Summary
    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) (1MBq, 1nmol per mouse). Pemetrexed (PMX, 400μg) was injected 1h prior to the radiofolate in order to reduce renal uptake. Images were acquired with a SPECT/CT camera 24h after injection of the radiofolate (40-50MBq, 3nmol 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 4h 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; 4h 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; 4h after injection) whereas the tumour uptake was retained (radiofolate 1 6.32±0.41%ID/g; radiofolate 2 8.99±0.43%ID/g; 4h 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