Current noninvasive tests for coronary artery disease detect atherosclerosis or regional ischemia. Global myocardial flow reserve is not routinely identified, although it may be an additional marker of disease development and progression. Methods: For the clinical work-up of suspected or known stable coronary artery disease, 275 individuals had undergone rest–dipyridamole ⁸²Rb myocardial perfusion imaging using PET. In addition to clinical measures of regional perfusion and function, an experimentally validated approach to quantify global myocardial flow reserve was used. Follow-up was obtained for 362 ± 277 d. Results: Myocardial blood flow and flow reserve showed significant correlation to systemic and cardiac hemodynamics and a weak association with risk factors such as age and history of hyperlipidemia. Flow reserve was expectedly lower in subjects with regional ischemia (1.70 ± 0.65 vs. 2.31 ± 0.97 in those without; P < 0.0001), but a wide range was observed in those without regional perfusion abnormalities. We used a composite endpoint of hard and soft events to determine that flow reserve below the median was predictive of adverse outcome in the overall population (P = 0.001) and in subjects with normal regional perfusion (n = 178; P = 0.036), whereas stress flow was predictive only in the overall population (P = 0.001). Age-adjusted multivariate analysis confirmed regional perfusion defects (relative hazard, 2.51; 95% confidence interval, 1.24–5.10; P = 0.009) and low global flow reserve (relative hazard, 2.93; 95% confidence interval, 1.30–6.65; P = 0.011) as independent predictors of cardiac events. Conclusion: In clinical cardiac ⁸²Rb PET, globally impaired flow reserve is a relevant marker for predicting short-term cardiovascular events. It may be used for integration with currently established functional and morphologic test results and for guidance of preventive measures, especially in the absence of regional flow–limiting disease.

Background— Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. ¹⁸ F-BMS-747158-02 ( ¹⁸ F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with ¹³ N-ammonia ( ¹³ NH ₃ ) and with radioactive microspheres in a pig model. Methods and Results— Fourteen pigs injected with 500 MBq of ¹³ NH ₃ or 100 to 200 MBq of ¹⁸ F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, ¹⁸ F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with ¹⁸ F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with ¹³ NH ₃ , ¹⁸ F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with ¹⁸ F-BMS PET showed good correlation ( r =0.88, slope=0.84) and agreement (mean difference −0.10 [25th percentile −0.3, 75th percentile 0.1 mL · min ⁻¹ · g ⁻¹ ]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL · min ⁻¹ · g ⁻¹ . The extent of defects induced by left anterior descending coronary artery constriction measured by ¹⁸ F-BMS and microspheres also correlated closely ( r =0.63, slope=1.1). Conclusions— ¹⁸ F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of ¹⁸ F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with ⁶⁸Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from ⁶⁸Ga- to ¹⁸F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite ⁶⁸Ge/⁶⁸Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, ¹⁸F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, ¹⁸F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging ¹⁸F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available ¹⁸F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.

PET allows for quantitative, regional myocardial perfusion imaging. The short half-lives of the perfusion tracers currently in use limit their clinical applicability. Here, the biodistribution and imaging quality of a new ¹⁸F-labeled myocardial perfusion agent (¹⁸F-BMS-747158-02) in an animal model are described. Methods: The biodistribution of ¹⁸F-BMS-747158-02 was determined at 10 and 60 min after injection. The first-pass extraction fraction of the tracer was measured in isolated rat hearts perfused with the Langendorff method. Small-animal PET imaging was used to study tracer retention. Results: The biodistribution at 10 min after injection demonstrated high myocardial uptake (3.1 percentage injected dose per gram [%ID/g]) accompanied by little activity in the lungs (0.3 %ID/g) and liver (1.0 %ID/g). The tracer showed a high and flow-independent myocardial first-pass extraction fraction, averaging 0.94 (SD = 0.04). PET imaging provided excellent delineation of myocardial structures. The heart-to-lung activity ratio increased from 4.7 to 10.2 between 1 and 15 min after tracer injection (at rest). Adenosine infusion (140 μg/kg/min) led to a significant increase in myocardial tracer retention (from 1.68 [SD = 0.23]) s⁻¹ to 3.21 [SD = 0.92] s⁻¹; P = 0.03). Conclusion: The observation of a high and flow-independent first-pass extraction fraction promises linearity between tracer uptake and myocardial blood flow. Sustained myocardial tracer uptake, combined with high image contrast, will allow for imaging protocols with tracer injection at peak exercise followed by delayed imaging. Thus, ¹⁸F-BMS-747158-02 is a promising new tracer for the quantitative imaging of myocardial perfusion and can be distributed to imaging laboratories without a cyclotron.

The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an ¹⁸F-labelled α_vβ₃ integrin antagonist (¹⁸F-Galacto-RGD) to monitor the integrin expression after myocardial infarction. Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial ¹⁸F-Galacto-RGD uptake at different time points following reperfusion. PET imaging and autoradiography demonstrated no significant focal myocardial ¹⁸F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 ± 0.22 vs. remote myocardium), peaked between 1 (3.43 ± 0.57) and 3 weeks (3.43 ± 0.95), and decreased to 1.96 ± 0.40 at 6 months after reperfusion. Pretreatment with α_vβ₃ integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis. Regional ¹⁸F-Galacto-RGD accumulation suggests up-regulation of α_vβ₃ integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.