Implementation of P22 Viral Capsids As Intravascular Magnetic Resonance <i>T</i>₁ Contrast Conjugates via Site-Selective Attachment of Gd(III)-Chelating Agents

P22 viral capsids and ferritin protein cages are utilized as templating macromolecules to conjugate Gd­(III)-chelating agent complexes, and we systematically investigates the effects of the macromolecules’ size and the conjugation positions of Gd­(III)-chelating agents on the magnetic resonance (MR) relaxivities and the resulting image contrasts. The relaxivity values of the Gd­(III)-chelating agent-conjugated P22 viral capsids (outer diameter: 64 nm) are dramatically increased as compared to both free Gd­(III)-chelating agents and Gd­(III)-chelating agent-conjugated ferritins (outer diameter: 12 nm), suggesting that the large sized P22 viral capsids exhibit a much slower tumbling rate, which results in a faster <i>T</i>₁ relaxation rate. Gd­(III)-chelating agents are attached to either the interior or exterior surface of P22 viral capsids and the conjugation positions of Gd­(III)-chelating agents, however, do not have a significant effect on the relaxivity values of the macromolecular conjugates. The contrast enhancement of Gd­(III)-chelating agent-conjugated P22 viral capsids is confirmed by in vitro phantom imaging at a short repetition times (TR) and the potential usage of Gd­(III)-chelating agent-conjugated P22 viral capsids for in vivo MR imaging is validated by visualizing a mouse’s intravascular system, including the carotid, mammary arteries, the jugular vein, and the superficial vessels of the head at an isotropic resolution of 250 μm

Implementation of P22 Viral Capsids As Intravascular Magnetic Resonance <i>T</i>₁ Contrast Conjugates via Site-Selective Attachment of Gd(III)-Chelating Agents

P22 viral capsids and ferritin protein cages are utilized as templating macromolecules to conjugate Gd­(III)-chelating agent complexes, and we systematically investigates the effects of the macromolecules’ size and the conjugation positions of Gd­(III)-chelating agents on the magnetic resonance (MR) relaxivities and the resulting image contrasts. The relaxivity values of the Gd­(III)-chelating agent-conjugated P22 viral capsids (outer diameter: 64 nm) are dramatically increased as compared to both free Gd­(III)-chelating agents and Gd­(III)-chelating agent-conjugated ferritins (outer diameter: 12 nm), suggesting that the large sized P22 viral capsids exhibit a much slower tumbling rate, which results in a faster <i>T</i>₁ relaxation rate. Gd­(III)-chelating agents are attached to either the interior or exterior surface of P22 viral capsids and the conjugation positions of Gd­(III)-chelating agents, however, do not have a significant effect on the relaxivity values of the macromolecular conjugates. The contrast enhancement of Gd­(III)-chelating agent-conjugated P22 viral capsids is confirmed by in vitro phantom imaging at a short repetition times (TR) and the potential usage of Gd­(III)-chelating agent-conjugated P22 viral capsids for in vivo MR imaging is validated by visualizing a mouse’s intravascular system, including the carotid, mammary arteries, the jugular vein, and the superficial vessels of the head at an isotropic resolution of 250 μm

Implementation of P22 Viral Capsids As Intravascular Magnetic Resonance <i>T</i>₁ Contrast Conjugates via Site-Selective Attachment of Gd(III)-Chelating Agents

P22 viral capsids and ferritin protein cages are utilized as templating macromolecules to conjugate Gd­(III)-chelating agent complexes, and we systematically investigates the effects of the macromolecules’ size and the conjugation positions of Gd­(III)-chelating agents on the magnetic resonance (MR) relaxivities and the resulting image contrasts. The relaxivity values of the Gd­(III)-chelating agent-conjugated P22 viral capsids (outer diameter: 64 nm) are dramatically increased as compared to both free Gd­(III)-chelating agents and Gd­(III)-chelating agent-conjugated ferritins (outer diameter: 12 nm), suggesting that the large sized P22 viral capsids exhibit a much slower tumbling rate, which results in a faster <i>T</i>₁ relaxation rate. Gd­(III)-chelating agents are attached to either the interior or exterior surface of P22 viral capsids and the conjugation positions of Gd­(III)-chelating agents, however, do not have a significant effect on the relaxivity values of the macromolecular conjugates. The contrast enhancement of Gd­(III)-chelating agent-conjugated P22 viral capsids is confirmed by in vitro phantom imaging at a short repetition times (TR) and the potential usage of Gd­(III)-chelating agent-conjugated P22 viral capsids for in vivo MR imaging is validated by visualizing a mouse’s intravascular system, including the carotid, mammary arteries, the jugular vein, and the superficial vessels of the head at an isotropic resolution of 250 μm

Layer-specific comparison of SIRs between STIM and NOSTIM in the primary auditory cor<i>t</i>ex.

<p>Mann-Whitney <i>U</i>-tests were used to compare the mean SIRs of Aud layers. The <i>z</i>-values were calculated from Mann-Whitney's <i>U</i>-values and their standard deviations. SIR is the normalized signal intensity of each ROI to its adjacent Temporalis muscles.</p><p>*<i>P</i><0.05.</p

Layer-specific comparison of SIRs between STIM and NOSTIM in the primary sensory cortex.

<p>Mann-Whitney <i>U</i>-tests were used to compare the mean SIRs of Sens layers. The <i>z</i>-values were calculated from Mann-Whitney's <i>U</i>-values and their standard deviations. SIR is the normalized signal intensity of each ROI to its adjacent Temporalis muscles.</p><p>*<i>P</i><0.05.</p

Comparison of SIRs between STIM and NOSTIM in the brain regions of auditory and olfactory pathways.

<p>Mann-Whitney <i>U</i>-tests were used to compare the mean SIRs of brain regions. The <i>z</i>-values were calculated from Mann-Whitney's <i>U</i>-values and their standard deviations. SIR is the normalized signal intensity of each ROI to its adjacent Temporalis muscles.</p><p>*<i>P</i><0.05.</p

Layer-specific comparison of SIRs between STIM and NOSTIM in the primary visual cortex.

<p>Mann-Whitney <i>U</i>-tests were used to compare the mean SIRs of Vis layers. The <i>z</i>-values were calculated from Mann-Whitney's <i>U</i>-values and their standard deviations. SIR is the normalized signal intensity of each ROI to its adjacent Temporalis muscles.</p><p>*<i>P</i><0.05.</p

Spearman's rank correlation maps between the mean SIRs of each layer in cortices.

<p>(A) Correlation map of Aud for NOSTIM (B) Correlation map of Aud for STIM (C) Correlation map of Sens for NOSTIM (D) Correlation map of Sens for STIM (E) Correlation map of Vis for NOSTIM (F) Correlation map of Vis for STIM. The correlation coefficient, ρ, is indicated with color maps ranging from blue to red; blue and red indicates the weakest and strongest correlation, respectively. A strong correlation between two layers indicates that the manganese accumulations in the two are likely to be linearly proportional to each other.</p