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Background: Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin αvβ3 is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [68Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters. Methods: First, the real-time interaction between [68Ga]Ga-RGD and integrin αvβ3 was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [68Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [68Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry. Results: SPR showed that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, forming a strong and stable binding. PET/CT showed a significantly higher uptake of [68Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [68Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = − 0.71, p < 0.001) after four weeks. Conclusion: This study demonstrates that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, which enables the evaluation of angiogenesis and remodeling. The [68Ga]Ga-RGD uptake after one week indicates that [68Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients. [ABSTRACT FROM AUTHOR]

Background: Myocardial perfusion imaging (MPI) using positron emission tomography (PET) tracers is an essential tool in investigating diseases and treatment responses in cardiology. 82Rubidium (82Rb)-PET imaging is advantageous for MPI due to its short half-life, but cannot be used for small animal research due to the long positron range. We aimed to correct for this, enabling MPI with 82Rb-PET in rats. Methods: The effect of positron range correction (PRC) on 82Rb-PET was examined using two phantoms and in vivo on rats. A NEMA NU-4-inspired phantom was used for image quality evaluation (%standard deviation (%SD), spillover ratio (SOR) and recovery coefficient (RC)). A cardiac phantom was used for assessing spatial resolution. Two rats underwent rest 82Rb-PET to optimize number of iterations, type of PRC and respiratory gating. Results: NEMA NU-4 metrics (no PRC vs PRC): %SD 0.087 versus 0.103; SOR (air) 0.022 versus 0.002, SOR (water) 0.059 versus 0.019; RC (3 mm) 0.219 versus 0.584, RC (4 mm) 0.300 versus 0.874, RC (5 mm) 0.357 versus 1.197. Cardiac phantom full width at half maximum (FWHM) and full width at tenth maximum (FWTM) (no PRC vs. PRC): FWTM 6.73 mm versus 3.26 mm (true: 3 mm), FWTM 9.27 mm versus 7.01 mm. The in vivo scans with respiratory gating had a homogeneous myocardium clearly distinguishable from the blood pool. Conclusion: PRC improved the spatial resolution for the phantoms and in vivo at the expense of slightly more noise. Combined with respiratory gating, the spatial resolution achieved using PRC should allow for quantitative MPI in small animals. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin is a cornerstone in lymphoma treatment, but is limited by dose-dependent cardiotoxicity. Rubidium-82 positron emission tomography (82Rb PET) assesses coronary microvascular function through absolute quantification of myocardial perfusion and myocardial perfusion reserve (MPR). Doxorubicin-induced microvascular injury represents a potential early marker of cardiotoxicity. Methods and results: We included 70 lymphoma patients scheduled for doxorubicin-based treatment. Cardiotoxicity was evaluated with 82Rb PET myocardial perfusion imaging during rest and adenosine stress before chemotherapy and shortly after the first doxorubicin exposure. Patients with a MPR decline > 20% were defined as having a low threshold for cardiotoxicity. In the 54 patients with complete data sets, MPR was significantly lower after the initial doxorubicin exposure (2.69 vs 2.51, P =.03). We registered a non-significant decline in stress perfusion (3.18 vs 3.02 ml/g/min, P =.08), but no change in resting myocardial perfusion. There were 13 patients with a low cardiotoxic threshold. These patients had a significantly higher age, but were otherwise similar to the remaining part of the study population. Conclusion: Decreases in MPR after initial doxorubicin exposure in lymphoma patients may represent an early marker of doxorubicin-induced cardiotoxicity. The prognostic value of acute doxorubicin-induced changes in MPR remains to be investigated. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin is the mainstay of curative lymphoma treatment but is associated with a dose-dependent cardiotoxicity that is often recognized too late to avoid substantial irreversible cardiac injury. Iodine-123 metaiodobenzylguanidine (123I-MIBG) is a gamma-emitting tracer that mimics noradrenaline uptake, storage, and release mechanisms in adrenergic presynaptic neurons. 123I-MIBG scintigraphy can be used for assessment of doxorubicin-induced injury to myocardial adrenergic neurons during treatment and could be the tool for early detection of doxorubicin cardiotoxicity, which is currently lacking.Methods and Results: A total of 37 lymphoma patients scheduled for doxorubicin treatment were included in our study. 123I-MIBG imaging was performed prior to chemotherapy and after a median of 4 cycles of doxorubicin. Early and late heart-to-mediastinum ratios (H/Mearly and H/Mlate) and washout rate (WOR) were used for evaluation of cardiotoxicity. The prognostic value of 123I-MIBG results was assessed using left ventricular ejection fraction (LVEF) as measured by cardiac magnetic resonance at 1-year follow-up. We found a post-therapy increase in WOR (including nine patients with > 10% increase), which was not statistically significant (18.6 vs 23.4%, P = 0.09). The difference appeared to be driven by an increase in H/Mearly. LVEF decreased from baseline to 1-year follow-up (64 vs 58%, P = 0.03). LVEF change was not associated with changes in WOR (P = 0.5).Conclusion: The present study does not provide evidence for 123I-MIBG imaging as a clinically applicable tool for early detection of doxorubicin-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Background: Small-animal myocardial infarct models are frequently used in the assessment of new cardioprotective strategies. A validated quantification of perfusion using a non-cyclotron-dependent PET tracer would be of importance in monitoring response to therapy. We tested whether myocardial PET perfusion imaging is feasible with Rubidium-82 (82Rb) in a small-animal scanner using a rat myocardial infarct model.Methods: 18 Sprague-Dawley rats underwent permanent coronary artery ligation (infarct group), and 11 rats underwent ischemia-reperfusion (reperfusion group) procedure. 82Rb-PET and magnetic resonance imaging (MRI) were conducted before and after the intervention. Perfusion was compared to both left ventricle ejection fraction (LVEF) and infarct size assessed by MRI.Results: Follow-up global 82Rb-uptake correlated significantly with infarct size (infarct group: r = -0.81, P < 0.001 and reperfusion group: r = -0.61, P = 0.04). Only 82Rb-uptake in the infarct group correlated with LVEF. At follow-up, a higher segmental 82Rb-uptake in the infarct group was associated with better wall motion (β = 0.034, CI [0.028;0.039], P < 0.001, R2 = 0.30), and inversely associated with scar transmurality (β = -2.4 [-2.6; -2.2], P < 0.001, R2 = 0.59). The associations were similar for the reperfusion group.Conclusion: 82Rb-PET is feasible in small animal scanners despite the long positron range and enables fast and time-efficient myocardial perfusion imaging in rat models. [ABSTRACT FROM AUTHOR]

Background: Assessment of infarct size after myocardial infarction is predictive of subsequent morphological changes and clinical outcome. This study aimed to assess subacute post-intervention Rubidium-82 (82Rb)-PET imaging in predicting left ventricle ejection fraction, regional wall motion, and final infarct size by CMR at 3-months after STEMI.Methods: STEMI patients undergoing percutaneous coronary intervention were included prospectively. Rest-only 82Rb-PET perfusion imaging was performed at median 36 hours [IQR: 22 to 50] after the treatment. The extent of hypoperfusion and absolute blood flow (mL·min·g) were estimated on a global and a 17-segment model with dedicated software. At 3-months follow-up patients completed the CMR functional and late gadolinium enhancement imaging.Results: 42 patients were included, but only 35 had follow-up CMR and constituted the study population. Absolute blood flow was significantly lower in the infarct-related territory compared to remote myocardium, P < .005. Extent of hypoperfusion correlated with final infarct size, r = 0.58, P < .001, while blood flow correlated with ejection fraction, r = 0.41, P < .05. In linear mixed models, higher subacute absolute blood flow (β = 4.6, confidence interval [3.5; 5.2], P < .001, R2 = 0.67) was associated with greater wall motion. Segmental extent of subacute hypoperfusion (β = 0.43 [0.38; 0.49], P < .001, R2 = 0.58) was associated with the degree of late gadolinium enhancement at 3-months.Conclusions: Subacute rest-only 82Rb-PET is feasible following STEMI and seems predictive of myocardial function and infarct size at 3-months. [ABSTRACT FROM AUTHOR]

Background: Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest 82Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR).Methods: Twelve STEMI patients were injected with 99mTc-Sestamibi intravenously immediate prior to reperfusion. SPECT, 82Rb-PET, and CMR imaging were performed post-reperfusion and at a 3-month follow-up. An automated algorithm determined area at risk, final infarct size, and hence myocardial salvage index.Results: SPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78).Conclusions: 82Rb-PET underestimates area at risk in patients with STEMI when compared to SPECT and CMR. However, our findings suggest that PET imaging seems feasible when assessing the clinical important parameters of final infarct size and myocardial salvage index, although with great variability, in a selected STEMI population with large infarcts. These findings should be confirmed in a larger population. [ABSTRACT FROM AUTHOR]

Background: HIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as a pathophysiological explanation. We compared the uptake of (18)F-fluorodeoxyglucose (FDG) by PET in four arterial regions, and factors associated with FDG uptake in well-treated HIV-infected patients without cardiovascular disease (CVD) and healthy controls.Methods and Results: We prospectively scanned 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers with FDG PET/CT, measuring standardized uptake values (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. We performed correlation analyses between FDG uptake and intima-media thickness (IMT), and soluble biomarkers of inflammation. We found no difference in arterial FDG uptake between the HIV-infected patients and healthy controls quantified either as mean SUVmax or target-to background ratio in the carotid region, the ascending aorta, the descending aorta, or the abdominal aorta. Correlations between SUV, IMT, and soluble biomarkers were scarce in both groups.Conclusion: In a group of optimally treated HIV-infected patients with full viral suppression, low Framingham risk score and no known CVD, we found no evidence of increased arterial inflammation as assessed by FDG PET/CT compared to healthy volunteers. [ABSTRACT FROM AUTHOR]