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. 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.
Current Cancer Drug Targets
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. 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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/1568009614666141020102337 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
P53 Family: At the Crossroads in Cancer Therapy
Current Medicinal Chemistry Metabotropic Glutamate Receptors in the Trafficking of Ionotropic Glutamate and GABAA Receptors at Central Synapses
Current Neuropharmacology Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease
Current Stem Cell Research & Therapy Nanobiotechnology-based Drug Delivery in Brain Targeting
Current Pharmaceutical Biotechnology Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions
Current Drug Targets Intraperitoneal Oncolytic and Tumor Vaccination Therapy with Replication-Competent Recombinant Virus: The Herpes Paradigm
Current Gene Therapy Perspectives in Biomolecular Therapeutic Intervention in Cancer: From the Early to the New Strategies With Type I Interferons
Current Medicinal Chemistry Cyclin-Dependent Kinase 4/6 (Cdk4/6) Inhibitors: Perspectives in Cancer Therapy and Imaging
Mini-Reviews in Medicinal Chemistry An Update of the Classical and Novel Methods Used for Measuring Fast Neurotransmitters During Normal and Brain Altered Function
Current Neuropharmacology TGF-β1 Signalling, Connecting Aberrant Inflammation and Colorectal Tumorigenesis
Current Pharmaceutical Design Detection and Specific Targeting of Hypoxic Regions within Solid Tumors: Current Preclinical and Clinical Strategies
Current Medicinal Chemistry Pyrimidine Nucleosides in Molecular PET Imaging of Tumor Proliferation
Current Medicinal Chemistry The Neuroprotective Effect of Ginkgo biloba Leaf Extract and its Possible Mechanism
Central Nervous System Agents in Medicinal Chemistry Tumor Suppression by DNA Base Excision Repair
Mini-Reviews in Medicinal Chemistry Armed Oncolytic Adenoviruses and Polymer-shielded Nanocomplex for Systemic Delivery
Current Cancer Therapy Reviews Strategies for Targeting Lentiviral Vectors
Current Gene Therapy Regulation by IFN-α/IFN-γ Co-Formulation (HerberPAG<sup>®</sup>) of Genes Involved in Interferon-STAT-Pathways and Apoptosis in U87MG
Current Topics in Medicinal Chemistry Immunotherapy of Malignant Gliomas Using Autologous and Allogeneic Tissue Cells
Anti-Cancer Agents in Medicinal Chemistry Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Current Drug Delivery Gallium-68: A New Trend in PET Radiopharmacy
Current Radiopharmaceuticals