LAT1 Targeted Delivery of Methionine Based Imaging Probe Derived from M(III) Metal Ions for Early Diagnosis of Proliferating Tumours using Molecular Imaging Modalities

Title:LAT1 Targeted Delivery of Methionine Based Imaging Probe Derived from M(III) Metal Ions for Early Diagnosis of Proliferating Tumours using Molecular Imaging Modalities

Volume: 14 Issue: 9

Author(s): Puja P. Hazari, Surbhi Prakash, Virendra K. Meena, Ambika Jaswal, Harleen Khurana, Surabhi K. Mishra, Hemanth kumar Somu Bhonsle, Lokendra Singh and Anil K. Mishra

Affiliation:

Keywords: Fluorescence, lanthanides, LAT1, MRI, methionine, PET Imaging.

Abstract: 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. K_D 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.

Cite this article as:

Hazari P. Puja, Prakash Surbhi, Meena K. Virendra, Jaswal Ambika, Khurana Harleen, Mishra K. Surabhi, Somu Bhonsle kumar Hemanth, Singh Lokendra and Mishra K. Anil, LAT1 Targeted Delivery of Methionine Based Imaging Probe Derived from M(III) Metal Ions for Early Diagnosis of Proliferating Tumours using Molecular Imaging Modalities, Current Cancer Drug Targets 2014; 14 (9) . https://dx.doi.org/10.2174/1568009614666141020102337