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The increased prevalence of obesity and its associated comorbidities has coincided with an upsurge in cardiometabolic diseases. Active tissue remodelling and fibrosis following cellular damage and inflammation, characterised by aberrant collagen deposition, is a common feature of cardiometabolic disease. Currently, there are no established probes for non-invasive whole-body imaging of active collagen biosynthesis to study the multisystem consequences of cardiometabolic diseases. We aimed to evaluate the potential of cis- and trans-4-[18F]fluoro-L-proline positron emission tomography (PET) as biomarkers of active misfolded and stable triple helical collagen biosynthesis, respectively, using a preclinical Western-style diet (WD)-induced rat model of cardiometabolic diseases. Here, we identified that correcting standard uptake values (SUV) for diet-induced alterations in plasma proline concentrations augmented trans- and cis-4-[18F]fluoro-L-proline PET outcome reporting. The most marked differences in uptake of trans-4-[18F]fluoro-L- proline were in the heart (mean±SEM SUVproline; 0.181±0.012) and liver (0.152±0.027) of animals fed the WD compared to age-matched controls (heart – 0.108±0.005, two-way ANOVA p<0.01; liver – 0.108±0.006, p<0.01). Increased uptake of trans-4-[18F]fluoro-L-proline positively correlated with histological accumulation of collagen, proline amino acid transporter expression, and diastolic dysfunction on echocardiography. Significantly greater cis-4-[18F]fluoro-L-proline uptake was detected in the heart of WD-fed animals compared to controls; however, there were no differences in the liver – implying there are organ-specific differences in misfolded collagen biosynthesis.Overall, our data suggests that [18F]fluoro-L-prolines are promising non-invasive systems-based imaging probes for multi-organ assessment of collagen biosynthesis in cardiometabolic diseases.