Figure 1: Principle of molecular imaging with CGRP-induced haemodynamic responses.

(a) CGRP acts on the heterodimeric G-protein coupled receptor RAMP1/CLR (left) to induce intracellular cAMP production, resulting in relaxation of vascular smooth muscle cells (VSMCs) and consequent vasodilation (middle). Dilation of microvasculature induces haemodynamic effects visible by MRI and other imaging methods (right). (b) Design for analyte-sensitive vasoactive probes comprising CGRP fused to a labile blocking domain via an analyte-responsive linker. Such probes can be activated by analytes that act sterically on the sensor to unblock the CGRP moiety, for example, by cleaving the blocking domain as shown here. This would induce an analyte-dependent haemodynamic response and enable molecular imaging with CGRP-based constructs. (c) Application of CGRP as a genetically encoded reporter would involve expressing prepro-CGRP in genetically modified cells or tissues. Subsequent processing of the construct should result in secreted CGRP, allowing the genetically modified cells to be tracked by haemodynamic imaging methods.