LAT1靶向投递M(III)金属离子衍生的蛋氨酸分子探针用于增生肿瘤早期诊断

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 Panwar Hazari, Surbhi Prakash, Virendra K. Meena, Ambika Jaswal, Harleen Khurana, Surabhi Kirti Mishra, Hemanth kumar Somu Bhonsle, Lokendra Singh and Anil K. Mishra

Affiliation:

关键词: 荧光，镧系，LAT1，蛋氨酸，PET成像。

摘要: 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:

Puja Panwar Hazari , Surbhi Prakash , Virendra K. Meena , Ambika Jaswal , Harleen Khurana , Surabhi Kirti Mishra , Hemanth kumar Somu Bhonsle , Lokendra Singh and Anil K. Mishra , 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