Statistical analyses of cardiac mass.

<p>Statistical analyses of cardiac mass.</p

Cardiac mass, structure and function parameters.

<p>* indicates variable analysed by Mann-Whitney U test.</p

Haemodynamic and vascular parameters.

<p>* indicates variables analysed by Mann-Whitney U test.</p

Statistical analyses of systolic blood pressure and vascular parameters.

<p>Statistical analyses of systolic blood pressure and vascular parameters.</p

Figure 1

<p>A–B. Scout cardiovascular magnetic resonance image of thoracic aorta demonstrating the planning of a transverse section through proximal descending aorta at the level of the right pulmonary artery. <b>C.</b> Arterial stiffness equations. Area(s) = systolic area, area(d) = diastolic area, ΔP = SBP-DBP, ρ = blood density (1059 kg.m⁻³).</p

Hypoxia-Responsive Cobalt Complexes in Tumor Spheroids: Laser Ablation Inductively Coupled Plasma Mass Spectrometry and Magnetic Resonance Imaging Studies

Dense tumors are resistant to conventional chemotherapies due to the unique tumor microenvironment characterized by hypoxic regions that promote cellular dormancy. Bioreductive drugs that are activated in response to this hypoxic environment are an attractive strategy for therapy with anticipated lower harmful side effects in normoxic healthy tissue. Cobalt bioreductive pro-drugs that selectively release toxic payloads upon reduction in hypoxic cells have shown great promise as anticancer agents. However, the bioreductive response in the tumor microenvironment must be better understood, as current techniques for monitoring bioreduction to Co­(II) such as X-ray absorption near-edge structure and extended X-ray absorption fine structure provide limited information on speciation and require synchrotron radiation sources. Here, we present magnetic resonance imaging (MRI) as an accessible and powerful technique to monitor bioreduction by treating the cobalt complex as an MRI contrast agent and monitoring the change in water signal induced by reduction from diamagnetic Co­(III) to paramagnetic Co­(II). Cobalt pro-drugs built upon the tris­(2-pyridylmethyl)­amine ligand scaffold with varying charge were investigated for distribution and activity in a 3D tumor spheroid model by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and MRI. In addition, paramagnetic ¹H NMR spectroscopy of spheroids enabled determination of the speciation of activated Co­(II)­TPAx complexes. This study demonstrates the utility of MRI and associated spectroscopy techniques for understanding bioreductive cobalt pro-drugs in the tumor microenvironment and has broader implications for monitoring paramagnetic metal-based therapies