LAT1 Targeted Delivery of Methionine Based Imaging Probe Derived from M(III) Metal Ions for Early Diagnosis of Proliferating Tumours using Molecular Imaging Modalities
Puja P. Hazari,
Virendra K. Meena,
Surabhi K. Mishra,
Hemanth kumar Somu Bhonsle,
Anil K. Mishra.
We investigated the potential of DTPA-bis(Methionine), a target specific amino acid based probe
for detection of L-type amino acid transporters (LAT1) known to over express in proliferating tumours using
multimodality imaging. The ligand, DTPA-bis(Met) was readily converted to lanthanide complexes and was
found capable of targeting cancer cells using multimodality imaging. DTPA-bis(Met) complexes were
synthesized and characterized by mass spectroscopy. MR longitudinal relaxivity, r1=4.067 ± 0.31 mM-1s-1
and transverse relaxivity, r2= 8.61 ± 0.07 mM-1s-1of Gd(III)-DTPA-bis(Met) were observed at pH 7.4 at 7T. Bright,
localized fluorescence of Eu(III)-DTPA-bis(Met) was observed with standard microscopy and displacement studies
indicated ligand functionality. KD value determined for Eu(III)-DTPA-bis(Met) on U-87MG cells was found to be 17.3
pM and showed appreciable fluorescence within the cells. Radio HPLC showed a radiochemical purity more than 95%
(specific activity = 400-500 MBq/μmol, labelling efficiency 78 %) for 68Ga(III)-DTPA-bis(Met). Pre-treatment of
xenografted U-87MG athymic mice with 68Ga(III)-DTPA-bis(Met) following unlabelled L-methionine administration
reduced tumour uptake by 10-folds in Micro PET. These data support the specific binding of 68Ga(III)-DTPA-bis(Met) to
the LAT1 transporter. To summarize, this agent possesses high stability in biological environment and exhibits effective
interaction with its LAT1 transporters giving high accumulation in tumour area, excellent tumour/non-tumour ratio and
low non-specific retention in vivo.
Keywords: Fluorescence, lanthanides, LAT1, MRI, methionine, PET Imaging.
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