Evidence map›Paper›PMID 25205462›Full record

ArticlePharmaceutical research2015

Metal based imaging probes of DO3A-Act-Met for LAT1 mediated methionine specific tumors: synthesis and preclinical evaluation.

K Ganesh Kadiyala, Anupama Datta, Jyoti Tanwar, Anupriya Adhikari, B S Hemanth Kumar, Krishna Chuttani, Meganathan Thirumal, Anil K Mishra

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Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

K Ganesh KadiyalaInstitute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S.K. Mazumdar Road, Delhi, 110054, India.
Anupama Datta
Jyoti Tanwar
Anupriya Adhikari
B S Hemanth Kumar
Krishna Chuttani
Meganathan Thirumal
Anil K Mishra

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTumor cells are known to have an elevated requirement for methionine due to increased protein synthesis and trans-methylation reactions. A methionine based macrocyclic tumor imaging system, DO3A-Act-Met, has been designed to provide a novel platform for tumor imaging via modalities, PET/MRI using metal ions, (68)Ga and (157)Gd.

methodsSynthesis of DO3A-Act-Met was confirmed through NMR and mass spectrometric techniques. Cytotoxicity of complexes was evaluated using MTT assay whereas receptor binding and trans-stimulation studies were performed on EAT and U-87 MG cell lines. Tumor targeting was assessed through imaging and biodistribution experiments on U-87 MG xenograft model.

resultsDO3A-Act-Met was synthesized and radiolabeled with (68)Ga in high radiochemical purity (85-92%). The receptor binding assay on EAT cells predicted high binding affinity with Kd of 0.78 nM. Efflux of (35)S-L-methionine trans-stimulated by extracellular DO3A-Act-Met on U-87MG cells suggested an L-system transport. MR studies revealed a longitudinal relaxivity of 4.35 mM(-1) s(-1) for Gd-DO3A-Act-Met and a 25% signal enhancement at tumor site. The biodistribution studies in U-87MG xenografts validated tumor specificity.

conclusionDO3A-Act-Met, a methionine conjugated probe is a promising agent for targeted molecular imaging, exhibiting high specificity towards tumor owing to its essential role in proliferation of cancer cells mediated through LAT1.

Indexed as

Contrast MediaCoordination ComplexesHeterocyclic Compounds, 1-RingMagnetic Resonance ImagingPositron-Emission TomographyRadiopharmaceuticalsAnimalsCell Line, TumorCell ProliferationCell SurvivalHumansLarge Neutral Amino Acid-Transporter 1MethionineMice, NudeMolecular ImagingMultimodal ImagingContrast MediaCoordination Complexesgadolinium 2,2',2'-(10-(2-(1-carboxy-3-(methylthio)propylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acidgallium 2,2',2'-(10-(2-(1-carboxy-3-(methylthio)propylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acidHeterocyclic Compounds, 1-RingLarge Neutral Amino Acid-Transporter 1MethionineRadiopharmaceuticals

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.