Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing; Yang, Jenny J.

doi:10.1039/c5nr09071g

Cited by 34 publications

(49 citation statements)

References 64 publications

(144 reference statements)

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“…Addition of the targeting moiety at the C-terminal of ProCA32 has little effect on the expression and folding of the protein variants. PEGylate the protein to improve its in vivo properties [23]. The incorporation of a PSMA-targeting peptide to ProCA32 with a flexible linker equips ProCA32 with PSMA-targeting capacity while maintaining high metal affinity and selectivity, as well as high relaxivities.…”

Section: Methodsmentioning

confidence: 99%

“…To ensure that the protein loaded to FPLC is completely apo- or Ca 2+ -free, incubate the supernatant with 20 mM EGTA for a few hours at 4 °C, and then inject into an FPLC for column binding [22, 23]. …”

Section: Notesmentioning

confidence: 99%

“…It is important to observe the gradual increase or decrease of luminescence signal until it reaches saturation [22, 23]. …”

Section: Notesmentioning

confidence: 99%

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Designing Calcium-Binding Proteins for Molecular MR Imaging

Salarian

Xue

Ibhagui

et al. 2019

Methods in Molecular Biology

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Early diagnosis, noninvasive detection, and staging of various diseases, remain one of the major clinical barriers to effective medical treatment and prevention of disease progression toward major clinical consequences. Molecular imaging technologies play an indispensable role in the clinical field in overcoming these major barriers. The increasing application of imaging techniques and agents in early detection of different diseases such as cancer has resulted in improved treatment response and clinical patient management. In this chapter we will first introduce criteria for the design and engineering of calcium-binding protein (CaBP) parvalbumin as a protein Gd-MRI contrast agent (ProCA) with unprecedented metal selectivity for Gd3+ over physiological metal ions. We will then discuss the further development of targeted MRI contrast agent for molecular imaging of PSMA biomarker for early detection of prostate cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Notesmentioning

confidence: 99%

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Designing Calcium-Binding Proteins for Molecular MR Imaging

Salarian

Xue

Ibhagui

et al. 2019

Methods in Molecular Biology

Self Cite

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“…It does not use ionizing radiation and can provide anatomical and functional information with high spatial and temporal resolution . Moreover, in the modern sciences and therapeutic medicine such as cancer tissue specificity, drug targeting or stem cell transplantation, it can be used for tracking of tumor metastasis, drug or cell ,,. MRI generates various images by measuring the magnetic relaxation times of distributed water molecules in tissues .…”

Section: Introductionmentioning

confidence: 99%

Preparation of Bio‐Inspired Melanin Nanoplatforms Chelated with Manganese Ions as a Potential T1 MRI Contrast Agent

2019

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Commercial contrast agents demonstrated release risk of the toxic gadolinium ions, and designing of highly stable complexes of biogenic element such as Mn is challenging. In this contribution, Mn‐melanin nanoparticles have been prepared and reacted with m‐PEG. The effect of initial amount of Mn ions on the Mn absorption and its release by melanin nanoparticles (MNP) has been investigated. It has been found that MNP absorb and release more Mn ion by increasing the initial amount of Mn ions. It has been found that time and temperature has no significant effect on Mn absorption by MNP. It is found that the hydrodynamic size of MNP is in accordance with size of MNP which measured with TEM analysis (5.5±2 nm) and the effect of chain of m‐PEG and conformational alteration of MNP is responsible of hydrodynamic size variation. The zeta potential of MNP is decreased by PEGylation and reaction with Mn ions. MNP−Mn‐PEG demonstrated low toxicity up to 3.45 mg/mL after 24 h for human embryonic kidney cells. Finally, the r1 value of MNP−Mn‐PEG is 10 fold higher than Dotarem as the commercial MRI contrast agent which can be administrated at much lower doses to achieve similar contrast of Dotarem.

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“…Very few examples of molecular agents exist in the literature that utilize a single Gd ion and effectively enhance a tumor target. 8–14 Most of these studies use either a change in MR signal derived from qualitative images or long acquisition times that do not allow for dynamic quantitative comparisons. Even fewer examples exist where these single Gd molecular agents have been subjected to quantitative MR techniques that allow for comparisons of sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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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Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

Cited by 34 publications

References 64 publications

Designing Calcium-Binding Proteins for Molecular MR Imaging

Designing Calcium-Binding Proteins for Molecular MR Imaging

Preparation of Bio‐Inspired Melanin Nanoplatforms Chelated with Manganese Ions as a Potential T1 MRI Contrast Agent

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

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