Non-oncological applications of RGD-based single-photon emission tomography and positron emission tomography agents

Ebenhan, Thomas; Kleynhans, Janke; Zeevaart, Jan Rijn; Jeong, Jae Min; Sathekge, Mike

doi:10.1007/s00259-020-04975-9

Cited by 9 publications

(6 citation statements)

References 154 publications

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“…The integrin-mediated cell adhesion/migration imaging with RGD PET was found to be involved in a wide range of pathophysiological processes, not only related to angiogenesis. Increased α v β 3 expression has been observed in some cancer cells as well as in cells involved in extracellular matrix remodeling such as fibroblasts and activated macrophages (8,9). However, the clinical relevance of such biomarker is not well understood (8).…”

Section: Introductionmentioning

confidence: 99%

“…However, the clinical relevance of such biomarker is not well understood (8). Although most studies using RGD-PET agents focused predominantly on tumorigenesis, a greater focus on nononcological applications such as cardiovascular diseases is of interest (9). In fact, in the development of atherosclerosis, expression of integrin α v β 3 has been found in endothelial cells as well as in CD68-positive macrophages, which are known as key factors in plaque instability (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Overview of the RGD-Based PET Agents Use in Patients With Cardiovascular Diseases: A Systematic Review

et al. 2022

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Studies using arginine–glycine–aspartate (RGD)-PET agents in cardiovascular diseases have been recently published. The aim of this systematic review was to perform an updated, evidence-based summary about the role of RGD-based PET agents in patients with cardiovascular diseases to better address future research in this setting. Original articles within the field of interest reporting the role of RGD-based PET agents in patients with cardiovascular diseases were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until October 26, 2021. Literature shows an increasing role of RGD-based PET agents in patients with cardiovascular diseases. Overall, two main topics emerged: the infarcted myocardium and atherosclerosis. The existing studies support that αvβ3 integrin expression in the infarcted myocardium is well evident in RGD PET/CT scans. RGD-based PET radiotracers accumulate at the site of infarction as early as 3 days and seem to be peaking at 1–3 weeks post myocardial infarction before decreasing, but only 1 study assessed serial changes of myocardial RGD-based PET uptake after ischemic events. RGD-based PET uptake in large vessels showed correlation with CT plaque burden, and increased signal was found in patients with prior cardiovascular events. In human atherosclerotic carotid plaques, increased PET signal was observed in stenotic compared with non-stenotic areas based on MR or CT angiography data. Histopathological analysis found a co-localization between tracer accumulation and areas of αvβ3 expression. Promising applications using RGD-based PET agents are emerging, such as prediction of remodeling processes in the infarcted myocardium or detection of active atherosclerosis, with potentially significant clinical impact.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overview of the RGD-Based PET Agents Use in Patients With Cardiovascular Diseases: A Systematic Review

et al. 2022

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“…By comparing 18 F-FPPRGD 2 and 18 F-FDG uptake values in various non-esophageal cancer patients, those authors showed no significant difference in tumor-to-background ratios between both tracers. The low RGD-based tracer uptake in several areas such as the lung, muscles, fat, the brain, or the myocardium could be an advantage for both qualitative and quantitative evaluation of thoracic, breast or brain lesions (Beer et al 2008 ; Minamimoto et al 2015 ), or for non-oncological applications such as cardiovascular imaging or inflammatory diseases (Dietz et al 2021 , 2022 ; Ebenhan et al 2021 ; Zhu et al 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Comparison of integrin αvβ3 expression with 68Ga-NODAGA-RGD PET/CT and glucose metabolism with 18F-FDG PET/CT in esophageal or gastroesophageal junction cancers

Dietz

Dunet

Mantziari

et al. 2023

European J Hybrid Imaging

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Background The 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. Methods Ten 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. Results 68Ga-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%). Conclusions In 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 registration: Trial registration: NCT02666547. Registered January 28, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02666547.

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“…It is difficult to predict the response after immunotherapy and evaluate the efficacy of immunotherapy with traditional imaging, but molecular imaging based on the integrin αvβ3 receptor may be an effective means for predicting and evaluating immunotherapy. In addition, non-oncology applications of RGD peptide-based SPECT imaging have been reported in the literature, showing exciting prospects and may become a hot topic for future research ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

Advances in Clinical Oncology Research on 99mTc-3PRGD2 SPECT Imaging

Xiao

Xin

2022

Front. Oncol.

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The integrin alpha(α)v beta(β)3 receptor is ubiquitous in malignant tumors and has a certain level of specificity for tumors. Technetium-99m hydrazinonicotinamide-dimeric cyclic arginyl-glycyl-aspartic acid peptide with three polyethylene glycol spacers (99mTc-3PRGD2) can bind specifically to the integrin αvβ3 receptor with high selectivity and strong affinity. Thus, it can specifically mark tumors and regions with angiogenesis for tumor detection and be used in single-photon emission computed tomography (SPECT) imaging. This modality has good application value for diagnosing and treating tumor lesions, such as those in the lung, breast, esophagus, head, and neck. This review provides an overview of the current clinical research progress of 99mTc-3PRGD2 SPECT imaging for tumor lesions, including for the diagnosis and differential diagnosis of tumors in different body parts, evaluation of related metastases, and evaluation of efficacy. In addition, the future clinical application prospects and possibilities of 99mTc-3PRGD2 SPECT imaging are further discussed.

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Non-oncological applications of RGD-based single-photon emission tomography and positron emission tomography agents

Cited by 9 publications

References 154 publications

Overview of the RGD-Based PET Agents Use in Patients With Cardiovascular Diseases: A Systematic Review

Overview of the RGD-Based PET Agents Use in Patients With Cardiovascular Diseases: A Systematic Review

Comparison of integrin αvβ3 expression with 68Ga-NODAGA-RGD PET/CT and glucose metabolism with 18F-FDG PET/CT in esophageal or gastroesophageal junction cancers

Advances in Clinical Oncology Research on 99mTc-3PRGD2 SPECT Imaging

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