68Ga-DOTA chelate, a novel imaging agent for assessment of myocardial perfusion and infarction detection in a rodent model

Autio, Anu; Uotila, Sauli; Kiugel, Max; Kytö, Ville; Liljenbäck, Heidi; Kudomi, Nobuyuki; Oikonen, Vesa; Metsälä, Olli; Helin, Semi; Knuuti, Juhani; Saraste, Antti; Roivainen, Anne

doi:10.1007/s12350-019-01752-6

Cited by 12 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the quest for increasing the potential of these imaging techniques, nuclides used as contrast agents like Gd, 18 F, 68 Ga [3] have become a crucial tool for revealing subtle differences between tissues allowing for enhanced accuracy of diagnosis and assessment of the effectiveness of therapies in the last decades.…”

Section: Introductionmentioning

confidence: 99%

Development of Superparamagnetic Nanoparticles Coated with Polyacrylic Acid and Aluminum Hydroxide as an Efficient Contrast Agent for Multimodal Imaging

et al. 2019

View full text Add to dashboard Cite

Early diagnosis of disease and follow-up of therapy is of vital importance for appropriate patient management since it allows rapid treatment, thereby reducing mortality and improving health and quality of life with lower expenditure for health care systems. New approaches include nanomedicine-based diagnosis combined with therapy. Nanoparticles (NPs), as contrast agents for in vivo diagnosis, have the advantage of combining several imaging agents that are visible using different modalities, thereby achieving high spatial resolution, high sensitivity, high specificity, morphological, and functional information. In this work, we present the development of aluminum hydroxide nanostructures embedded with polyacrylic acid (PAA) coated iron oxide superparamagnetic nanoparticles, Fe3O4@Al(OH)3, synthesized by a two-step co-precipitation and forced hydrolysis method, their physicochemical characterization and first biomedical studies as dual magnetic resonance imaging (MRI)/positron emission tomography (PET) contrast agents for cell imaging. The so-prepared NPs are size-controlled, with diameters below 250 nm, completely and homogeneously coated with an Al(OH)3 phase over the magnetite cores, superparamagnetic with high saturation magnetization value (Ms = 63 emu/g-Fe3O4), and porous at the surface with a chemical affinity for fluoride ion adsorption. The suitability as MRI and PET contrast agents was tested showing high transversal relaxivity (r2) (83.6 mM−1 s−1) and rapid uptake of 18F-labeled fluoride ions as a PET tracer. The loading stability with 18F-fluoride was tested in longitudinal experiments using water, buffer, and cell culture media. Even though the stability of the 18F-label varied, it remained stable under all conditions. A first in vivo experiment indicates the suitability of Fe3O4@Al(OH)3 nanoparticles as a dual contrast agent for sensitive short-term (PET) and high-resolution long-term imaging (MRI).

show abstract

Section: Introductionmentioning

confidence: 99%

Development of Superparamagnetic Nanoparticles Coated with Polyacrylic Acid and Aluminum Hydroxide as an Efficient Contrast Agent for Multimodal Imaging

et al. 2019

View full text Add to dashboard Cite

show abstract

“… 43 We do not have access to a cyclotron in line with our PET and substituted the classical [ 15 O]H 2 O flow tracer to 68 Ga-DOTA which has not been validated for abdominal organ perfusion. While it is effective in measurement of the perfusion of the heart 15 and lung, 30 the properties of this tracer could account for the substantial reduction in K1 compared with the more modest impairment reported in obese versus lean patients using the [ 15 O]H 2 O method. Similarly, this may explain why the reported perfusion of abdominal fat in animals and humans was reduced.…”

Section: Discussionmentioning

confidence: 99%

“…Since a reduction in GLP-1r binding potential could also be the consequence of hyperglycemia 10 and/or hyperinsulinemia, 14 we determined the effect of hyperinsulinemia during euglycemia by administration of a GLP-1r radioactive agonist during the plateau of a euglycemic–hyperinsulinemic clamp in both lean and obese animals. 68 Ga-DOTA 15 distribution was used concomitantly to quantify blood flow, which could affect the binding potential without altering receptor affinity. 16 We performed our experiments in miniature obese and lean Yucatan adult pigs in whom relative spatial resolution is higher even when compared with that obtained in rats using a dedicated miniature positron emission tomography (PET) imager.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs

Malbert

Chauvin

Horowitz

2020

BMJ Open Diab Res Care

View full text Add to dashboard Cite

IntroductionThe insulinotropic capacity of exogenous glucagon like peptide-1 (GLP-1) is reduced in type 2 diabetes and the insulin-resistant obese. We have tested the hypothesis that this response is the consequence of a reduced pancreatic GLP-1 receptor (GLP-1r) density in insulin-resistant obese animals.Research design and methodsGLP-1r density was measured in lean and insulin-resistant adult miniature pigs after the administration of a 68Ga-labeled GLP-1r agonist. The effect of hyperinsulinemia on GLP-1r was assessed using sequential positron emission tomography (PET), both in the fasted state and during a clamp. The impact of tissue perfusion, which could account for changes in GLP-1r agonist uptake, was also investigated using 68Ga-DOTA imaging.ResultsGLP-1r binding potential in the obese pancreas was reduced by 75% compared with lean animals. Similar reductions were evident for fat tissue, but not for the duodenum. In the lean group, induced hyperinsulinemia reduced pancreatic GLP-1r density to a level comparable with that of the obese group. The reduction in blood to tissue transfer of the GLP-1r ligand paralleled that of tissue perfusion estimated using 68Ga-DOTA.ConclusionsThese observations establish that a reduction in abdominal tissue perfusion and a lower GLP-1r density account for the diminished insulinotropic effect of GLP-1 agonists in type 2 diabetes.

show abstract

“…Conventional PET imaging has usually been limited to a single tracer per scan. Therefore, in order to perform PET examinations with multiple tracers on the same patient, different scans should be performed sequentially if the half-life of one tracer is short enough (i.e., tracers based on 13 N, 15 O, or 82 Rb) to allow fast clearance of the tracer before the next tracer is administered. Otherwise, scans can be performed in different days.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, clinically promising isotopes like 68 Ga [8], which has a very low branching ratio for the extra gamma photons, can be combined with other regular isotopes like 18 F. The proposed methodology was implemented and validated in pigs by a combination of two tracers for cardiac PET imaging, namely 68 Ga-DOTA and 18 FDG. While 18 FDG is a very well-known tracer used in myocardial viability studies among other cardiac applications [9], 68 Ga-DOTA has been recently proposed as a new PET tracer for MBF and extracellular volume fraction (ECV) determination [10][11][12][13] as well as for pulmonary blood flow [14].…”

Section: Introductionmentioning

confidence: 99%

Explicit measurement of multi-tracer arterial input function for PET imaging using blood sampling spectroscopy

et al. 2020

View full text Add to dashboard Cite

Background: Conventional PET imaging has usually been limited to a single tracer per scan. We propose a new technique for multi-tracer PET imaging that uses dynamic imaging and multi-tracer compartment modeling including an explicitly derived arterial input function (AIF) for each tracer using blood sampling spectroscopy. For that purpose, at least one of the co-injected tracers must be based on a non-pure positron emitter. Methods: The proposed technique was validated in vivo by performing cardiac PET/ CT studies on three healthy pigs injected with 18 FDG (viability) and 68 Ga-DOTA (myocardial blood flow and extracellular volume fraction) during the same acquisition. Blood samples were collected during the PET scan, and separated AIF for each tracer was obtained by spectroscopic analysis. A multi-tracer compartment model was applied to the myocardium in order to obtain the distribution of each tracer at the end of the PET scan. Relative activities of both tracers and tracer uptake were obtained and compared with the values obtained by ex vivo analysis of excised myocardial tissue segments. Results: A high correlation was obtained between multi-tracer PET results, and those obtained from ex vivo analysis (18 FDG relative activity: r = 0.95, p < 0.0001; SUV: r = 0.98, p < 0.0001). Conclusions: The proposed technique allows performing PET scans with two tracers during the same acquisition obtaining separate information for each tracer.

show abstract

68Ga-DOTA chelate, a novel imaging agent for assessment of myocardial perfusion and infarction detection in a rodent model

Cited by 12 publications

References 23 publications

Development of Superparamagnetic Nanoparticles Coated with Polyacrylic Acid and Aluminum Hydroxide as an Efficient Contrast Agent for Multimodal Imaging

Development of Superparamagnetic Nanoparticles Coated with Polyacrylic Acid and Aluminum Hydroxide as an Efficient Contrast Agent for Multimodal Imaging

Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs

Explicit measurement of multi-tracer arterial input function for PET imaging using blood sampling spectroscopy

Contact Info

Product

Resources

About