Dataset Information

[⁶⁸Ga]Ga-NODAGA-E[(cRGDyK)]₂ angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

ABSTRACT:

Background

Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin α_vβ₃ 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 α_vβ₃ 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 α_vβ₃, 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 α_vβ₃, 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.

SUBMITTER: Bentsen S

PROVIDER: S-EPMC10558373 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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[<sup>68</sup>Ga]Ga-NODAGA-E[(cRGDyK)]<sub>2</sub> angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

Bentsen Simon S Jensen Jacob Kildevang JK Christensen Esben E Petersen Lars Ringgaard LR Grandjean Constance Eline CE Follin Bjarke B Madsen Johanne Straarup JS Christensen Camilla C Clemmensen Andreas A Binderup Tina T Hasbak Philip P Ripa Rasmus Sejersten RS Kjaer Andreas A

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 20230501 5

<h4>Background</h4>Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin α<sub>v</sub>β<sub>3</sub> 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 [<sup>68</sup>Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters.<h4>Methods</h4>First, the real-time interaction between [<sup>68</sup>Ga] ...[more]

PMID: 37127725

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Project description:Integrin αvβ3, a subtype of the arginine-glycine-aspartate (RGD)-recognizing cell surface integrins, is upregulated on endothelial cells during angiogenesis and on tumor cells. Because of involvement in tumor growth, invasiveness and metastases, and angiogenesis, integrin αvβ3 is an attractive target in cancers. In this study, we applied 68Ga-NODAGA-E[c(RGDyK)]2 for imaging of integrin αvβ3 in patients with neuroendocrine neoplasms (NENs) and its potential use for prognostication. We hypothesized that 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT would show tumor lesion uptake and that higher tumor lesion uptake was associated with a poorer prognosis. Methods: Between December 2017 and November 2020 we prospectively enrolled 113 patients with NEN of all grades (2019 World Health Organization classification) for 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT. The scan was acquired 45 min after injection of 200 MBq of 68Ga-NODAGA-E[c(RGDyK)]2 Board-certified specialists in nuclear medicine and radiology analyzed the PET/CT measuring SUVmax in tumor lesions. Positive tumor lesions were defined as those with tumor-to-liver background ≥ 2. Maximal tumor SUVmax for each patient was used as a predictor of outcome. Patients were followed for at least 1 y to assess progression-free survival and overall survival. Results: Of 113 patients enrolled in the trial, 99 underwent 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT, with 97 patients having evaluable lesions. The patients predominantly had small intestinal (64%) or pancreatic (20%) NEN and most had metastatic disease (93%). Most patients had low-grade tumors (78%), whereas 22% had high-grade tumors. During a median follow-up of 31 mo (interquartile range, 26-38 mo), 62 patients (64%) experienced disease progression and 25 (26%) patients died. In total, 76% of patients had positive tumor lesions, and of the patients with high-grade tumors 91% had positive tumor lesions. High integrin αvβ3 expression, defined as an SUVmax of at least 5.25, had a hazard ratio of 2.11 (95% CI, 1.18-3.78) and 6.95 (95% CI, 1.64-29.51) for progression-free survival and overall survival, respectively (P = 0.01 for both). Conclusion: Tumor lesion uptake of 68Ga-NODAGA-E[c(RGDyK)]2 was evident in patients with all grades of NEN. High uptake was associated with a poorer prognosis. Further studies are warranted to establish whether 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT may become a prediction tool for identification of patients eligible for treatments targeting integrin αvβ3.

Project description:BackgroundThe primary aims of this study were to compare in patients with esophageal or esophagogastric junction cancers the potential of 68Ga-NODAGA-RGD PET/CT with that of 18F-FDG PET/CT regarding tumoral uptake and distribution, as well as histopathologic examination.MethodsTen 68Ga-NODAGA-RGD and ten 18F-FDG PET/CT were performed in nine prospectively included participants (1 woman; aged 58 ± 8.4 y, range 40-69 y). Maximum SUV (SUVmax) and metabolic tumor volumes (MTV) were calculated. The Mann-Whitney U test and Spearman correlation analysis (ρ) were used.Results68Ga-NODAGA-RGD PET/CT detected positive uptake in 10 primary sites (8 for primary tumors and 2 for local relapse suspicion), 6 lymph nodes and 3 skeletal sites. 18F-FDG PET/CT detected positive uptake in the same sites but also in 16 additional lymph nodes and 1 adrenal gland. On a lesion-based analysis, SUVmax of 18F-FDG was significantly higher than those of 68Ga-NODAGA-RGD (4.9 [3.7-11.3] vs. 3.2 [2.6-4.2] g/mL, p = 0.014). Only one participant showed a higher SUVmax in an osseous metastasis with 68Ga-NODAGA-RGD as compared to 18F-FDG (6.6 vs. 3.9 g/mL). Correlation analysis showed positive correlation between 18F-FDG and 68Ga-NODAGA-RGD PET parameters (ρ = 0.56, p = 0.012 for SUVmax, ρ = 0.78, p < 0.001 for lesion-to-background ratios and ρ = 0.58, p = 0.024 for MTV). We observed that 18F-FDG uptake was homogenous inside all the confirmed primary sites (n = 9). In contrast, 68Ga-NODAGA-RGD PET showed more heterogenous uptake in 6 out of the 9 confirmed primary sites (67%), seen mostly in the periphery of the tumor in 5 out of the 9 confirmed primary sites (56%), and showed slight extensions into perilesional structures in 5 out of the 9 confirmed primary sites (56%).ConclusionsIn conclusion, 68Ga-NODAGA-RGD has lower potential in the detection of esophageal or esophagogastric junction malignancies compared to 18F-FDG. However, the results suggest that PET imaging of integrin αvβ3 expression may provide complementary information and could aid in tumor diversity and delineation.Trial registrationTrial registration: NCT02666547. Registered January 28, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02666547 .

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Dataset Information

[⁶⁸Ga]Ga-NODAGA-E[(cRGDyK)]₂ angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

Background

Methods

Results

Conclusion

Publications

[<sup>68</sup>Ga]Ga-NODAGA-E[(cRGDyK)]<sub>2</sub> angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

[68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

Background

Methods

Results

Conclusion

Publications

[<sup>68</sup>Ga]Ga-NODAGA-E[(cRGDyK)]<sub>2</sub> angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

[⁶⁸Ga]Ga-NODAGA-E[(cRGDyK)]₂ angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.