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

  • Cristina MüllerEmail author
  • Thomas L. Mindt
  • Marion de Jong
  • Roger Schibli
Original Article



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.


DOTA-folate Pemetrexed Folate receptor SPECT/CT 177Lu 



We thank Dr. Christian Lackas and Dr. Nils Schramm for support with the NanoSPECT/CT (Bioscan).


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Cristina Müller
    • 1
    • 2
    Email author
  • Thomas L. Mindt
    • 3
  • Marion de Jong
    • 2
  • Roger Schibli
    • 1
    • 3
  1. 1.Center for Radiopharmaceutical Science ETH-PSI-USZPaul Scherrer InstituteVilligen PSISwitzerland
  2. 2.Department of Nuclear MedicineErasmus MCRotterdamThe Netherlands
  3. 3.Department of Chemistry and Applied BiosciencesETH ZurichZurichSwitzerland

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