Assessment of insulin sensitivity <i>in vivo</i> in control and diabetic mice with a radioactive tracer of glucose transport: [<sup>125</sup>I]‐6‐deoxy‐6‐iodo‐<scp>D</scp>‐glucose

Perret, Pascale; Ghezzi, Cathérine; Mathieu, Jean‐Paul; Morin, Christophe; Fagret, Daniel

doi:10.1002/dmrr.382

Cited by 12 publications

(6 citation statements)

References 30 publications

(38 reference statements)

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“…Plasma. As previously observed in rodents, 12,13 plasma clearance and blood clearance were superimposable (data not shown). Circulating 123 I-6DIG activity increased twice during the complete protocol following each bolus-injection prior to quickly decreasing ( Fig.…”

Section: Pharmacokinetics Clearance and Metabolitessupporting

confidence: 87%

“…9,10 We previously validated the 6-deoxy-6-iodo-D-glucose (6DIG) as an iodinated tracer of glucose transport with a biological behavior similar to that of 3-OMG. 11,12 We demonstrated the in vivo feasibility of IR assessment with 123/125 I-6DIG in mice and rats 13,14 and then developed an experimental protocol allowing the assessment of cardiac IR in rats without the need for an euglycemic hyperinsulinemic-clamp. 15 The aim of the present study was to evaluate the safety, biodistribution and dosimetry of the 123 I-6DIG injection in healthy and diabetic volunteers in order to proceed with the clinical translation of the methodology previously validated preclinically.…”

Section: Introductionmentioning

confidence: 99%

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Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers

et al. 2019

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Purpose Insulin resistance is a key feature of the metabolic syndrome and type 2 diabetes, in which noninvasive assessment is not currently allowed by any methodology. We previously validated an iodinated tracer of glucose transport (6DIG) and a new methodology for the in vivo quantification of cardiac insulin resistance in rodents. The aim of this study was to investigate the safety, biodistribution, and radiation dosimetry of this method using 123I-6DIG in 5 healthy and 6 diabetic volunteers. Methods The collection of adverse effects (AEs) and medical supervision of vital parameters and biological variables allowed the safety evaluation. Biodistribution was studied by sequentially acquiring whole-body images at 1, 2, 4, 8, and 24 hours postinjection. The total number of disintegrations in each organ normalized to the injected activity was calculated as the area under the time-activity curves. Dosimetry calculations were performed using OLINDA/EXM. Results No major adverse events were observed. The average dose corresponding to the 2 injections of 123I-6DIG used in the protocol was 182.1 ± 7.5 MBq. A fast blood clearance of 123I-6DIG was observed. The main route of elimination was urinary, with greater than 50% of urine activity over 24 hours. No blood or urine metabolite was detected. 123I-6DIG accumulation mostly occurred in elimination organs such as kidneys and liver. Mean radiation dosimetry calculations indicated an effective whole-body absorbed dose of 3.35 ± 0.57 mSv for the whole procedure. Conclusions 123I-6DIG was well tolerated in human with a dosimetry profile comparable to that of other commonly used iodinated tracers, thereby allowing further clinical development of the tracer.

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Section: Pharmacokinetics Clearance and Metabolitessupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers

et al. 2019

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“…[ 123 I]6-deoxy-6-iodo-D-glucose (6 123 IDG) was also recently proposed as a possible tracer (13). It was reported to be responsive to insulin in in vitro preparations, although not in isolated rat heart, and able to detect a defect in glucose transport in diabetic mice (25), although not in diabetic rats (17). Additionally, 6 123 IDG was excreted in large amounts into the bladder within minutes after injection (17).…”

mentioning

confidence: 99%

6-Fluoro-6-deoxy-d-glucose as a tracer of glucose transport

Landau¹,

Spring-Robinson²,

Muzic³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Glucose transport rates are estimated noninvasively in physiological and pathological states by kinetic imaging using PET. The glucose analog most often used is (18)F-labeled 2FDG. Compared with glucose, 2FDG is poorly transported by intestine and kidney. We examined the possible use of 6FDG as a tracer of glucose transport. Lacking a hydroxyl at its 6th position, 6FDG cannot be phosphorylated as 2FDG is. Prior studies have shown that 6FDG competes with glucose for transport in yeast and is actively transported by intestine. Its uptake by muscle has been reported to be unresponsive to insulin, but that study is suspect. We found that insulin stimulated 6FDG uptake 1.6-fold in 3T3-L1 adipocytes and azide stimulated the uptake 3.7-fold in Clone 9 cells. Stimulations of the uptake of 3OMG, commonly used in transport assays, were similar, and the uptakes were inhibited by cyclochalasin B. Glucose transport is by GLUT1 and GLUT4 transporters in 3T3-L1 adipocyte and by the GLUT1 transporter in Clone 9 cells. Cytochalasin B inhibits those transporters. Rats were also imaged in vivo by PET using 6(18)FDG. There was no excretion of (18)F into the urinary bladder unless phlorizin, an inhibitor of active renal transport, was also injected. (18)F activity in brain, liver, and heart over the time of scanning reached a constant level, in keeping with the 6FDG being distributed in body water. In contrast, (18)F from 2(18)FDG was excreted in relatively large amounts into the bladder, and (18)F activity rose with time in heart and brain in accord with accumulation of 2(18)FDG-6-P in those organs. We conclude that 6FDG is actively transported by kidney as well as intestine and is insulin responsive. In trace quantity, it appears to be distributed in body water unchanged. These results provide support for its use as a valid tracer of glucose transport.

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“…Our group then proposed to use 6DIG in vivo to assess insulin resistance by nuclear imaging. Studies in diabetic mice db/db and in insulin resistant fructose-fed rats showed that 6DIG was able to assess glucose transport defects in vivo (Slimani et al, 2002;Perret et al, 2003. In a preliminary study, we have shown in different rat models of insulin resistance that 6DIG could be used to assess non-invasively, using nuclear NaI probes, different degrees of cardiac insulin resistance without using hyperinsulinaemic clamp (Figure 3).…”

Section: I]-6-deoxy-6-iodo-d-glucose (6dig)mentioning

confidence: 99%

Nuclear Imaging of Glucose Transport/Metabolism – An Interesting Tool to Screen Insulin Resistance, Refine Diagnosis of Type 2 Diabetes, Understand Disease Mechanisms, and/or Evaluate New Therapies

Perret¹,

Henri²,

Slimani³

et al. 2011

Medical Complications of Type 2 Diabetes

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Assessment of insulin sensitivity in vivo in control and diabetic mice with a radioactive tracer of glucose transport: [¹²⁵I]‐6‐deoxy‐6‐iodo‐D‐glucose

Cited by 12 publications

References 30 publications

Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers

Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers

6-Fluoro-6-deoxy-d-glucose as a tracer of glucose transport

Nuclear Imaging of Glucose Transport/Metabolism – An Interesting Tool to Screen Insulin Resistance, Refine Diagnosis of Type 2 Diabetes, Understand Disease Mechanisms, and/or Evaluate New Therapies

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Assessment of insulin sensitivity in vivo in control and diabetic mice with a radioactive tracer of glucose transport: [125I]‐6‐deoxy‐6‐iodo‐D‐glucose

Cited by 12 publications

References 30 publications

Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers

Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers

6-Fluoro-6-deoxy-d-glucose as a tracer of glucose transport

Nuclear Imaging of Glucose Transport/Metabolism – An Interesting Tool to Screen Insulin Resistance, Refine Diagnosis of Type 2 Diabetes, Understand Disease Mechanisms, and/or Evaluate New Therapies

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Assessment of insulin sensitivity in vivo in control and diabetic mice with a radioactive tracer of glucose transport: [¹²⁵I]‐6‐deoxy‐6‐iodo‐D‐glucose