[68Ga]‐HP‐DO3A‐nitroimidazole: a promising agent for PET detection of tumor hypoxia. (29th June 2015)

• Record Type: Journal Article
• Authors: Wu, Yunkou; Hao, Guiyang; Ramezani, Saleh; Saha, Debabrata; Zhao, Dawen; Sun, Xiankai; Sherry, A. Dean
• Is Part Of: Contrast media & molecular imaging. Volume 10:Number 6(2015:Nov./Dec.)
• Page Start: 465
• Page End: 472
• Publication Date: 2015-06-29
• Subjects: tumor hypoxia -- 68Ga -- PET -- nitroimidazole; Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1649
• Languages: English
• ISSNs: 1555-4309

Abstract

Abstract : The goal of this study is to evaluate a new 68 Ga‐based imaging agent for detecting tumor hypoxia using positron emission tomography (PET). The new hypoxia targeting agent reported here, [ 68 Ga]‐HP‐DO3A‐nitroimidazole ([ 68 Ga]‐HP‐DO3A‐NI), was constructed by linking a nitroimidazole moiety with the macrocyclic ligand component of ProHance®, HP‐DO3A. The hypoxia targeting capability of this agent was evaluated in A549 lung cancer cells in vitro and in SCID mice bearing subcutaneous A549 tumor xenografts. The cellular uptake assays showed that significantly more [ 68 Ga]‐HP‐DO3A‐NI accumulates in hypoxic tumor cells at 30, 60 and 120 min than in the same cells exposed to 21% O2 . The agent also accumulated in hypoxic tumors in vivo to give a tumor/muscle ratio (T/M) of 5.0 ± 1.2 ( n = 3) as measured by PET at 2 h post‐injection (p.i.). This was further confirmed by ex vivo biodistribution data. In addition, [ 68 Ga]‐HP‐DO3A‐NI displayed very favorable pharmacokinetic properties, as it was cleared largely through the kidneys with little to no accumulation in liver, heart or lung (%ID/g < 0.5%) at 2 h p.i. The specificity of the agent for hypoxic tissues was further validated in a comparative study with a control compound, [ 68 Ga]‐HP‐DO3A, which lacks the nitroimidazole moiety, and by PET imaging of tumor‐bearing mice breathing air versus 100% O2 . Given the commercial availability of cGMP 68 Ge/ 68 Ga generators and the ease of 68 Ga labeling, the new agent could potentially be widely applied for imaging tumor hypoxia prior to radiation therapy. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : [ 68 Ga]‐HP‐DO3A‐NI shows considerable promise as a new hypoxia PET tracer, as it displays very favorable pharmacokinetic properties in vivo .