Back to Search
Start Over
Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy.
- Source :
-
European Journal of Nuclear Medicine & Molecular Imaging . Jun2009, Vol. 36 Issue 6, p938-946. 9p. 1 Color Photograph, 1 Diagram, 3 Charts, 1 Graph. - Publication Year :
- 2009
-
Abstract
- 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. 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). 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. 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MICE
*RADIOISOTOPES
*XENOGRAFTS
*THERAPEUTICS
*TUMORS
*MEDICAL radiology
Subjects
Details
- Language :
- English
- ISSN :
- 16197070
- Volume :
- 36
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- European Journal of Nuclear Medicine & Molecular Imaging
- Publication Type :
- Academic Journal
- Accession number :
- 39242961
- Full Text :
- https://doi.org/10.1007/s00259-008-1058-9