Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

Herrmann, K; Johansen, Mette L.; Craig, Sonya E.L.; Vincent, Jason; Howell, Michael D.; Gao, Ying; Lu, Lihua; Erokwu, Bernadette O.; Agnes, Richard S.; Zhang, Lu; Pokorski, Jonathan K.; Basilion, James P.; Gulani, Vikas; Griswold, Mark A.; Flask, Chris A.; Brady‐Kalnay, Susann M.

doi:10.3390/diagnostics5030318

Cited by 15 publications

(39 citation statements)

References 18 publications

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“…84 A quantitative MRI study recently conducted demonstrates a sustained binding of SBK2 to tumors over time compared with conventional contrast agents with an approximate 2:1 TNR 45-60 minutes after injection. 85 Toxicity, dosage, and efficacy of the PTPμ-directed agents still needs to be tested in humans, but these preliminary studies are encouraging, especially considering the high level of tumor margin labeling. Human studies are being planned.…”

Section: Targeted Fluorescent Molecular Imaging Agentsmentioning

confidence: 99%

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

et al. 2016

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The median life expectancy following a diagnosis of glioblastoma (GBM) is 15 months. While chemotherapeutics may someday cure GBM by killing the highly dispersive malignant cells, the most important contribution that clinicians can currently offer to improve survival is by maximizing the extent of resection and providing concurrent chemo-radiation, which has become standard. Strides have been made in this area with the advent and implementation of methods of improved intraoperative tumor visualization. One of these techniques, optical fluorescent imaging with targeted molecular imaging agents, allows the surgeon to view fluorescently labeled tumor tissue during surgery with the use of special microscopy – thereby highlighting where to resect, and indicating when tumor-free margins have been obtained. This advantage is especially important at the difficult to observe margins where tumor cells infiltrate normal tissue. Targeted fluorescent agents also may be valuable for identifying tumor versus non-tumor tissue. In this review, we briefly summarize non-targeted fluorescent tumor imaging agents before discussing several novel targeted fluorescent agents being developed for glioma imaging in the context of fluorescent guided surgery or live molecular navigation. Many of these agents are currently undergoing preclinical testing. As the agents become available, however, it is necessary to understand the strengths and weaknesses of each.

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Section: Targeted Fluorescent Molecular Imaging Agentsmentioning

confidence: 99%

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

et al. 2016

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“…6 For this in vitro study, 100 signal averages were acquired for determination of the agent relaxivities ( r 1 ). The T 1 relaxivities were obtained by measuring a dilution series of two lots of each agent on three separate occasions using saline as the diluent.…”

Section: Methodsmentioning

confidence: 99%

“…4–7 Previous studies using heterotopic glioma xenograft models demonstrated that a PTPμ-targeted MRI agent with 3 Gd chelates labeled flank tumors more effectively than non-specific contrast agents. 5,6 The chelator used was the polydentate ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). A dynamic, quantitative T 1 mapping strategy was implemented to objectively evaluate the in vivo intra-tumoral concentration of the PTPμ-targeted contrast agent [SBK2-Tris-(Gd-DOTA) 3 ] over time.…”

Section: Introductionmentioning

confidence: 99%

“…6 This effect required a dose of 0.2mmol Gd/kg, twice the dose typically used for clinical agents. 6 Enhanced intra-tumoral retention was indicated by the percent change in T 1 value as well as by calculations of local Gd concentration. 6 …”

Section: Introductionmentioning

confidence: 99%

“…6 Enhanced intra-tumoral retention was indicated by the percent change in T 1 value as well as by calculations of local Gd concentration. 6 …”

Section: Introductionmentioning

confidence: 99%

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Quantitative Molecular Imaging with a Single Gd-Based Contrast Agent Reveals Specific Tumor Binding and Retention in Vivo

et al. 2017

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Magnetic Resonance Imaging (MRI) has become an indispensable tool in the diagnosis and treatment of many diseases, especially cancer. However, the poor sensitivity of MRI relative to other imaging modalities, such as PET, has hindered the development and clinical use of molecular MRI contrast agents that could provide vital diagnostic information by specifically locating a molecular target altered in the disease process. This work describes the specific and sustained in vivo binding and retention of a protein tyrosine phosphatase mu (PTPμ)-targeted, molecular MR contrast agent with a single gadolinium (Gd) chelate using a quantitative MRI T1 mapping technique in glioma xenografts. Quantitative T1 mapping is an imaging method used to measure the longitudinal relaxation time, the T1 relaxation time, of protons in a magnetic field after excitation by a radiofrequency pulse. T1 relaxation times can in turn be used to calculate the concentration of a gadolinium-containing contrast agent in a region of interest, thereby allowing the retention or clearance of an agent to be quantified. In this context, retention is a measure of molecular contrast agent binding. Using conventional peptide chemistry, a PTPmu-targeted peptide was linked to a chelator that had been conjugated to a lysine residue. Following complexation with Gd, this PTPmu-targeted molecular contrast agent containing a single Gd ion showed significant tumor enhancement and a sustained increase in Gd concentration in both heterotopic and orthotopic tumors using dynamic quantitative MRI. This single Gd-containing PTPmu agent was more effective than our previous version with three Gd ions. Differences between non-specific and specific agents, due to specific tumor binding, can be determined within the first 30 minutes after agent administration by examining clearance rates. This more facile chemistry, when combined with quantitative MR techniques, allows for widespread adoption by academic and commercial entities in the field of molecular MRI ultimately leading to improved detection of disease.

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A preparation pulse for fast steady state approach in Actual Flip angle Imaging

et al. 2023

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BackgroundActual Flip angle Imaging (AFI) is a sequence used for B1 mapping, also embedded in the Variable flip angle with AFI for simultaneous estimation of T1, B1 and equilibrium magnetization.PurposeTo investigate the design of a preparation module for AFI to allow a fast approach to steady state (SS) without requiring the use of dummy acquisitions.MethodsThe features of a preparation module with a B1 insensitive adiabatic pulse, spoiler gradients, and a recovery time were studied with simulations and validated via experiments and acquired with different k‐space traveling strategies. The robustness of the flip angle of the preparation pulse on the acquired signal is studied.ResultsWhen a 90° adiabatic pulse is used, the forthcoming can be expressed as a function of repetition times and AFI flip angle only as , where n represents the ratio between the two repetition times of AFI. The robustness of the method is demonstrated by showing that using the values further away from 90° still allows for a faster approach to SS than the use of dummy pulses.ConclusionsThe preparation module is particularly advantageous for low flip angles, as well as for AFI sequences that sample the center of the k‐space early in the sequence, such as centric ordering acquisitions, and for ultrafast EPI‐based AFI methods, thus allowing to reduce scanner overhead time.

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Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

Cited by 15 publications

References 18 publications

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

Quantitative Molecular Imaging with a Single Gd-Based Contrast Agent Reveals Specific Tumor Binding and Retention in Vivo

A preparation pulse for fast steady state approach in Actual Flip angle Imaging

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