Establishment of a method for in-vivo SPECT/CT imaging analysis of 111In-labeled exendin-4 pancreatic uptake in mice without the need for nephrectomy or a secondary probe

Hamamatsu, Keita; Fujimoto, Hiroyuki; Fujita, Naotaka; Murakami, Takaaki; Kimura, Hiroyuki; Saji, Hideo; Inagaki, Nobuya

doi:10.1016/j.nucmedbio.2018.06.002

Cited by 14 publications

(35 citation statements)

References 18 publications

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“…In vivo 111 In-Ex4 SPECT/CT in RCS-10 mice The pancreata of RCS-10 mice were visualized by 111 In-Ex4 SPECT/CT, as described in the previous reports 14,17,18 . Representative images of in vivo 111 In-Ex4 SPECT/CT are shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Ex vivo pancreas analysis using the 111 In-exendin-4 probe The 111 In-exendin-4 probe, (Lys12[In-BnDTPA-Ahx])exendin-4 ( 111 In-Ex4) was synthesized, as previously reported 9 . Although the utility of 111 In-Ex4 for in vivo SPECT/computed tomography (CT) imaging was established in the previous report 14,17,18 , the pancreatic visualization of 10-week-old male RCS-10 mice was reconfirmed before the investigation in dulaglutide-treated mice. The SPECT/CT imaging was carried out using a Triumph LabPET12/SPECT4/CT (TriFoil Imaging Inc., Chatsworth, CA, USA), as previously reported 14 .…”

Section: Oral Glucose Tolerance Test and Mice Glycohemoglobin Measurementioning

confidence: 99%

“…Although the utility of 111 In-Ex4 for in vivo SPECT/computed tomography (CT) imaging was established in the previous report 14,17,18 , the pancreatic visualization of 10-week-old male RCS-10 mice was reconfirmed before the investigation in dulaglutide-treated mice. The SPECT/CT imaging was carried out using a Triumph LabPET12/SPECT4/CT (TriFoil Imaging Inc., Chatsworth, CA, USA), as previously reported 14 . Two weeks after the last administration of dulaglutide (day 35), mice were injected through the tail vein with 111 In-Ex4 (3.0 MBq/mouse).…”

Section: Oral Glucose Tolerance Test and Mice Glycohemoglobin Measurementioning

confidence: 99%

“…For the purpose of visualization and quantification of b-cells, GLP-1R-targeted imaging methods, such as single-photon emission computed tomography (SPECT) and positron emission tomography have recently emerged [8][9][10][11] . These methods were developed for the detection of insulinoma and transplanted islets, and the evaluation of b-cell mass [12][13][14] , and they have not been used for clinical prediction of drug efficacy in diabetes treatment. Using these methods in the present study, we investigated factors that might be related to the determination of in vivo GLP-1RA efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Association of glucagon‐like peptide‐1 receptor‐targeted imaging probe with in vivo glucagon‐like peptide‐1 receptor agonist glucose‐lowering effects

Murakami

Fujimoto

Fujita

et al. 2020

J of Diabetes Invest

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Aims/Introduction Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients do not respond well to the therapy, and caution must be taken for certain patients, including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP‐1RA therapy. GLP‐1R‐targeted imaging has recently emerged to visualize and quantify β‐cells. We investigated whether GLP‐1R‐targeted imaging can predict the efficacy of GLP‐1RA treatment. Materials and Methods We developed 111 Indium‐labeled exendin‐4 derivative ( 111 In‐Ex4) as a GLP‐1R‐targeting probe. Diabetic mice were selected from NONcNZO10/LtJ male mice that were fed for different durations with 11% fat chow. After 3‐week administration of dulaglutide as GLP‐1RA therapy, mice with non‐fasting blood glucose levels <300 mg/dL and >300 mg/dL were defined as responders and non‐responders, respectively. In addition, ex vivo 111 In‐Ex4 pancreatic accumulations ( 111 In‐Ex4 pancreatic values) were examined. Results The non‐fasting blood glucose levels after treatment were 172.5 ± 42.4 mg/dL in responders ( n = 4) and 330.8 ± 20.7 mg/dL in non‐responders ( n = 5), respectively. Ex vivo 111 In‐Ex4 pancreatic values showed significant correlations with post‐treatment glycohemoglobin and glucose area under curve during an oral glucose tolerance test ( R 2 = 0.76 and 0.80; P < 0.01 and <0.01, respectively). The receiver operating characteristic area under curve for identifying responders by ex vivo 111 In‐Ex4 pancreatic values was 1.00 ( P < 0.01). Conclusion Ex vivo 111 In‐Ex4 pancreatic values reflected dulaglutide efficacy, suggesting clinical possibilities for expanding GLP‐1R‐targeted imaging applications.

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Section: Resultsmentioning

confidence: 99%

Section: Oral Glucose Tolerance Test and Mice Glycohemoglobin Measurementioning

confidence: 99%

Section: Oral Glucose Tolerance Test and Mice Glycohemoglobin Measurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association of glucagon‐like peptide‐1 receptor‐targeted imaging probe with in vivo glucagon‐like peptide‐1 receptor agonist glucose‐lowering effects

Murakami

Fujimoto

Fujita

et al. 2020

J of Diabetes Invest

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“…This resulted in mean volumes of pancreas selected for analysis in the first and second SPECT scans of 182 and 173 mm 3 , respectively. We have previously reported that analyzing more than 40% of the volume of the whole pancreas is necessary for an accurate estimate of the radioactivity for the whole pancreas (31). The mean pancreatic area selected for the analysis of the second SPECT scans in the present study was 76.0% of the whole pancreas.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive longitudinal quantification of β‐cell mass with [¹¹¹In]‐labeled exendin‐4

et al. 2019

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Currently, quantifying β‐cell mass (BCM) requires harvesting the pancreas. In this study, we investigated a potential noninvasive method to quantify BCM changes longitudinally using [Lys12(111In‐BnDTPA‐Ahx)] exendin‐4 ([111In]‐Ex4) and single‐photon emission computed tomography (SPECT). We used autoradiography and transgenic mice expressing green fluorescent protein under the control of mouse insulin 1 gene promotor to evaluate the specificity of [111In]‐Ex4 toward β cells. Using nonobese diabetic (NOD) mice, we injected [111In]‐Ex4 (3.0 MBq) intravenously and performed SPECT 30 min later, repeating this at a 2‐wk interval. After the second scan, we harvested the pancreas and calculated BCM from immunohistochemically stained pancreatic sections. Specific accumulation of [111In]‐Ex4 in β cells was confirmed by autoradiography, with a significant correlation (r = 0.94) between the fluorescent and radioactive signal intensities. The radioactive signal from the pancreas in the second SPECT scan significantly correlated (r = 0.89) with BCM calculated from the immunostained pancreatic sections. We developed a regression formula to estimate BCM from the radioactive signals from the pancreas in SPECT scans. BCM can be quantified longitudinally and noninvasively by SPECT imaging with [111In]‐Ex4. This technique successfully demonstrated longitudinal changes in BCM in NOD mice before and after onset of hyperglycemia.—Fujita, N., Fujimoto, H., Hamamatsu, K., Murakami, T., Kimura, H., Toyoda, K., Saji, H., Inagaki, N. Noninvasive longitudinal quantification of β‐cell mass with [111In]‐labeled exendin‐4. FASEB J. 33, 11836‐11844 (2019). http://www.fasebj.org

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Development of novel radioiodinated exendin-4 derivatives targeting GLP-1 receptor for detection of β-cell mass

Ogawa

Kimura

Fujimoto

et al. 2021

Bioorganic & Medicinal Chemistry

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Establishment of a method for in-vivo SPECT/CT imaging analysis of 111In-labeled exendin-4 pancreatic uptake in mice without the need for nephrectomy or a secondary probe

Cited by 14 publications

References 18 publications

Association of glucagon‐like peptide‐1 receptor‐targeted imaging probe with in vivo glucagon‐like peptide‐1 receptor agonist glucose‐lowering effects

Association of glucagon‐like peptide‐1 receptor‐targeted imaging probe with in vivo glucagon‐like peptide‐1 receptor agonist glucose‐lowering effects

Noninvasive longitudinal quantification of β‐cell mass with [¹¹¹In]‐labeled exendin‐4

Development of novel radioiodinated exendin-4 derivatives targeting GLP-1 receptor for detection of β-cell mass

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