Imaging sigma-1 receptor (S1R) expression using iodine-124-labeled 1-(4-iodophenyl)-3-(2-adamantyl)guanidine ([(124)I]IPAG) Journal Article
| Authors: | Gangangari, K. K.; Váradi, A.; Majumdar, S.; Larson, S. M.; Pasternak, G. W.; Pillarsetty, N. V. K. |
| Article Title: | Imaging sigma-1 receptor (S1R) expression using iodine-124-labeled 1-(4-iodophenyl)-3-(2-adamantyl)guanidine ([(124)I]IPAG) |
| Abstract: | Purpose: Sigma-1 receptors (S1Rs) are overexpressed in almost all human cancers, especially in breast cancers. 1-(4-Iodophenyl)-3-(2-adamantyl)guanidine (IPAG) is a validated high-affinity S1R antagonist. The objective of the current study is to evaluate the potential of iodine-124-labeled IPAG ([124I]IPAG) to image S1R-overexpressing tumors. Procedures: [124I]IPAG was synthesized from a tributyltin precursor dissolved in ethanol using chloramine-T as oxidant. Purity was analyzed using HPLC. In vitro and in vivo studies were performed using the breast cancer cell line MCF-7. Competitive inhibition studies were performed using haloperidol and cold IPAG. Tumors were established in athymic nude mice by injecting 107 cells subcutaneously. Mice were imaged on micro-positron emission tomography (PET) at 4, 24, 48, 72, and 144 h post i.v. injection. Biodistribution studies were performed at same time points. In vivo tracer dilution studies were performed using excess of IPAG and haloperidol. The efficacy of [124I]IPAG to image tumors was evaluated in LNCaP tumor–bearing mice as well. Results: [124I]IPAG was synthesized in quantitative yield and in vitro studies indicated that [124I]IPAG binding was specific to S1R. PET imaging studies in MCF7 tumor–bearing mice reveal that [124I]IPAG accumulates in tumor and is preferentially retained while clearing from non-target organs. The tumor to background increases with time, and tumors could be clearly visualized starting from 24 h post administration. Similar results were obtained in mice bearing LNCaP tumors. In vivo tracer dilution studies showed that the uptake of [124I]IPAG could be competitively inhibited by excess of IPAG and haloperidol. Conclusions: [124I]IPAG was synthesized successfully in high yields, and in vitro and in vivo studies demonstrate specificity of [124I]IPAG. [124I]IPAG shows specific accumulation in tumors with increasing tumor to background ratio at later time points and therefore has high potential for imaging S1R-overexpressing cancers. © 2019, World Molecular Imaging Society. |
| Keywords: | controlled study; unclassified drug; drug efficacy; nonhuman; positron emission tomography; mouse; breast cancer; haloperidol; animal experiment; animal model; in vivo study; drug potency; in vitro study; tumor xenograft; drug screening; molecular imaging; drug synthesis; prostate cancer; drug distribution; radioactivity; pet imaging; high performance liquid chromatography; competitive inhibition; sigma 1 opiate receptor; iodine-124; female; priority journal; article; lncap cell line; ic50; sigma-1 receptor; mcf-7 cell line; biodistribution studies; [124i]ipag; [131i]ipag; 1 (2 adamantyl) 3 (4 iodophenyl)guanidine; 1 (2 adamantyl) 3 (4 iodophenyl)guanidine i 124; haloperidol hydrochloride; sigma receptor antagonist |
| Journal Title: | Molecular Imaging and Biology |
| Volume: | 22 |
| Issue: | 2 |
| ISSN: | 1536-1632 |
| Publisher: | Springer |
| Date Published: | 2020-04-01 |
| Start Page: | 358 |
| End Page: | 366 |
| Language: | English |
| DOI: | 10.1007/s11307-019-01369-8 |
| PUBMED: | 31165385 |
| PROVIDER: | scopus |
| PMCID: | PMC6893110 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2020 -- Source: Scopus |
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133Pillarsetty -
959Larson -
54Majumdar -
414Pasternak -
13Varadi -
11Gangangari
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