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

Müller, Cristina and Mindt, Thomas L. and de Jong, Marion and Schibli, Roger. (2009) Evaluation of a novel radiofolate in tumour-bearing mice : promising prospects for folate-based radionuclide therapy. European journal of nuclear medicine and molecular imaging, Vol. 36. pp. 938-946.

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Official URL: http://edoc.unibas.ch/dok/A6005056

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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 (111)InCl(3) and (177)LuCl(3), 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 (111)In-DOTA-folate (radiofolate 1) or (177)Lu-DOTA-folate (radiofolate 2) (1 MBq, 1 nmol per mouse). Pemetrexed (PMX, 400 microg) 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.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Radiologische Chemie (Mindt)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Radiologische Chemie (Mindt)
UniBasel Contributors:Mindt, Thomas L.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:0340-6997
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:22
Deposited On:24 May 2013 09:05

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