Πυρηνική Ιατρική και Σακχαρώδης Διαβήτης. Nεφρική λειτουργία Γαστρική κινητικότητα Μοριακή απεικόνιση :

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1 Πυρηνική Ιατρική και Σακχαρώδης Διαβήτης Nεφρική λειτουργία Γαστρική κινητικότητα Μοριακή απεικόνιση : Εκλεκτικές σχέσεις Πυρηνικής Ιατρικής και Σακχαρώδη Διαβήτη Γ. Αρσος Γ Εργ. Πυρηνικής Ιατρικής ΑΠΘ, ΓΝ Παπαγεωργίου

2 GFR : Glomerular filtration rate GFR is widely accepted as the best index of kidney function in health and disease, and accurate values are needed for optimal decision making in many clinical settings Stevens LA & Levey AS, JASN 2009

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4 Go AS et al, N Engl J Med 2004

5 GFR - SCr relationship : 1/SCr = SCr GFR = 27.0 GFR R = 0.86, P < n = 2626 age : 4 mo 88 yrs BSA : m 2 SCr : mg/dl R = 0.83, P < GFR : ml/min/1.73 m 2

6 Urea Plasma / Serum Creatinine Cystatin C Creatinine Mean of Urea + Creatinine levels clearance endo Inulin Clearance ex exo Radiotracer clearance ( 51 Cr-EDTA, 99m Tc-DTPA, 125 I-Iothalamate) Non-radioactive contrast agent clearance (Iohexol) Demographics GFR prediction equations

7 Measurement of glomerular filtration-rate in man using a 51Cr-edetic-acid complex Garnett ES et al, Lancet 1967

8 GFR measurement : By plasma clearance of exogenous tracer according to the British Society of Nuclear Medicine Guidelines 2005 Bolus i.v. injection of 3.7 MBq Cr-51-EDTA 2 plasma samples at 120 and 240 min p.i. statistically adequate counting slope-intercept method of data analysis Brochner-Mortensen correction Indexation by body surface area (Haycock) GFR in ml/min/1.73 m 2 Flemming J et al, NMC 2005

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10 Drug nephrotoxicity Chemotherapy dosing Misleading SCr High risk patients (single kidney, RVD, renal transplant) Difficult 24 h clearance (elderly, learning difficulties) - Potential live kidney donors Evaluation / follow-up of renal function in chronic GNP (HUS, DM) Stevens LA et al, JASN 2009 mgfr : βάση κατασκευής προβλεπτικών εξισώσεων egfr (CG, MDRD, CKD-EPI) - Single kidney function evaluation - (in conjunction with relative renal function measurements from radionuclide imaging) Fleming JS et al, NMC, 2005

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12 Role of age, sex, ethnicity, muscularity on PCr levels & egfr

13 Levey AS et al. Ann Intern Med, 1999

14 Inker LA et al. NEJM, 2012

15 Levey AS et al. Ann Intern Med, 2009

16 egfr mgfr (ml/min/1.73 sqm) ANOVA, p< < >90 GFR (ml/min/1.73 sqm) The mean egfr mgfr differences over various GFR increments (<60, and 90 ml/min/1.73 m 2 ) Arsos G et al, EJNMMI 2006

17 Nephropathy in Diabetes Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the U.S. and Europe; this is due to the facts that 1) diabetes, particularly type 2, is increasing in prevalence 2) diabetes patients now live longer 3) patients with diabetic ESRD are now being accepted for treatment in ESRD programs where formerly they had been excluded ADA, Diabetes Care 2004

18 In newly diagnosed type 2 diabetic patients, particularly those with a GFR >90 ml/min per 1.73m 2, both CG and MDRD equations significantly underestimate igfr. This highlights a limitation in the use of egfr in the majority of diabetic subjects outside the setting of chronic kidney disease. Chudleigh RA et al. Diabetes Care, 2007

19 In patients with type 2 diabetes, egfrcys do not currently provide better egfr than egfrcre. Iliadis F et al. Diabetologia, 2011

20 Silveiro SP et al. Diabetes Care, 2011

21 de Boer IH et al. J Am Soc Nephrol, 2014

22 MacIsaac RJ et al. BMC Nephrol, 2015

23 Gastrointestinal Complications of Diabetes Esophageal involvement heartburn dysphagia Gastroparesis early satiety nausea vomiting bloating postprandial fullness upper abdominal pain 5-12% in DM intestinal enteropathy diarrhea constipation fecal incontinence nonalcoholic fatty liver disease

24 Elbert EC, Dis Mon 2005

25 Biphasic nature of gastric emptying Siegel JA et al, Gut 1988,

26 Gastroparesis diabeticorum vs delayed gastric emptying GPD : the clinical syndrome characterized by a significant impairment of gastric emptying in the absence of mechanical obstruction accompanied by severe nausea, vomiting, malnutrition, and often weight loss DGE : even in healthy individuals with artificially induced hyperglycaemia Samsom M et al, Gut 1997] diabetic autonomic neuropathy hyperglycemia

27 Insulin-Induced Hypoglycemia Accelerates Gastric Emptying of Solids and Liquids in Long-Standing Type 1 Diabetes Russo A et al, J Clin Endocrinol Metab 2005

28 Prokinetic drugs for diabetic gastroparesis Elbert EC, Dis Mon 2005

29 Uncontrolled diabetes mellitus due to gastroparesis diabeticorum: treatment with metoclopramide Before Rx After Rx 5 hrs 24 hrs 3 hrs Muls EE et al, Postgrad Med J 1981

30 American Family Physician Shakil et al 2008

31 Methodologies for assessing emptying Gastric emptying scintigraphy = the gold standard 99m Tc-sulfur colloid and 111 In DTPA Solid/Liquid meals physiologic, quantitative, non-invasive 13 C-octanoate breath test 13 CO 2 in exhaled air // gastric emptying non-invasive, cost-effective, non-radioactive (MS, NMRS) - indirect, intact liver-lung function Ultrasonography emptying, transpyloric flow of liquid gastric contents accommodation in proximal stomach MRI differentiate : solid/liquid phases/gastric secretion/air SmartPill non-digestible capsule records luminal ph, temperature, pressure during gastrointestinal transit (gastric emptying time)

32 Comparison of gastric emptying measurement methodologies Samsom M et al, Diabetes Metab Res Rev 2009

33 Consensus Report on Gastric Emptying: What s Needed to Prevent Tarnishing a Gold Standard? Although gastric-emptying scintigraphy in most clinical practices is the gold standard for measuring gastric motility, there has been concern that it will lose its role to other competing modalities because of a lack of standardization Maurer A, J Nucl Med Technol 2008

34 percent gastric retention Assessment of gastric emptying using a low fat meal: establishment of international control values time (hours) median 95th percentile Gastric retention >10% at 4 h is indicative of delayed emptying Tougas G et al, Am J Gastrenterol 2000

35 SNM Procedure Guideline for Adult Solid-Meal Gastric-Emptying Study Donohoe JK et al, J Nucl Med Technol 2009

36 SNM Procedure Guideline for Adult Solid-Meal Gastric-Emptying Study Min 4 hrs NPO (ideally NPO from midnight -> test in the morning) Diabetic patients : good control, glucose < 200 mg/dl Premenopausal women : days 1 10 of the cycle Prokinetic agents : metoclopramide, tegaserod, domperidone, erythromycin stopped 2 d before the test (unless efficacy test) Medications that delay gastric emptying : Opiates, antispasmodic agents stopped 2 d before testing Other medications : atropine, nifedipine, progesterone, octreotide, theophylline, benzodiazepine Donohoe JK et al, J Nucl Med Technol 2009

37 SNM Procedure Guideline for Adult Solid-Meal Gastric-Emptying Study 1. Related diseases a. Hiatal hernia b. Gastroesophageal reflux c. Esophageal motility disorders (e.g., achalasia, scleroderma, diffuse esophageal spasm, stricture 2. Previous interventions a. Medications : cisapride, metoclopramide, domperidone, erythromycin b. Surgery Donohoe JK et al, J Nucl Med Technol 2009

38 SNM Procedure Guideline for Adult Solid-Meal Gastric-Emptying Study Recommended meal: a. 118 ml of liquid egg whites b. Two slices of toasted white bread c. 30 g of jam or jelly d. 120 ml of water Meal preparation: Mix MBq (0.5 1 mci) of 99m Tc-sulfur colloid into the liquid egg whites Donohoe JK et al, J Nucl Med Technol 2009

39 SNM Procedure Guideline for Adult Solid-Meal Gastric-Emptying Study Imaging GP/LEHR collimator, 128x128 image matrix ANT + POST (LAO) planar images distal esophagus, stomach, proximal small bowel 1 min immediately after ingestion of the meal (t 0 ) Repeated images at 2, 3, 4 hours Processing ROIs Geometric mean : (ANTcts x POSTcts) 1/2 Gastric retention : percentage of counts at t 0 Donohoe JK et al, J Nucl Med Technol 2009

40 SNM Procedure Guideline for Adult Solid-Meal Gastric-Emptying Study 1. Vomiting after meal 2. Poor labeling 3. A nonstandard meal 4. Environmental variation (noise, lighting, temperature) 5. Emotional fluctuations 6. Nausea due to unfamiliar meal 7. Food intake before the study 8. Slow eating 9. Gastroesophageal reflux 10. Overlap of small-bowel activity with the stomach ROI 11. Lack of attenuation correction particularly in obese patients 13. Failure of the patient to eate the entire meal 14. Lack of decay correction Donohoe JK et al, J Nucl Med Technol 2009

41 % ΓΑΣΤΡΙΚΟΥ ΠΕΡΙΕΧΟΜΕΝΟΥ % of ANT counts at t0 ANT POST GM 99,4 36,6 60,3 99,9 35,3 59, ,0 32,2 58, ,0 30,9 56, ,4 29,9 56,4 106,5 30,0 56,5 113,6 28,6 57, time (min) POST ANT 110,1 27,6 55, ,3 25,6 53,6 Τ1/2 = 145 min 103,3 27,6 53,4 80 r = ,8 25,7 49, ,5 22,5 43, ,0 11,6 25, ,4 9,1 17,9 21,4 4,3 9, ΧΡΌΝΟΣ (min)

42 0 20 ANT POST

43 ant post 0 240

44 SNM Procedure Guideline for Adult Solid-Meal Gastric-Emptying Study Donohoe JK et al, J Nucl Med Technol 2009

45 120 Gastric emptying T1/2 = 115 min time (min)

46 5/1999, προ θεραπείας 3/2000, υπό θεραπεία 2/2001, υπό θεραπεία O min O min O min 21O min 2O9 min 230 min

47 % γαστρικής πλήρωσης % γαστρικής πλήρωσης % γαστρικής πλήρωσης 5/1999 πρo θεραπείας Τ1/2 =? 5/1999 πρo θεραπείας /2000 υπό θεραπεία χρόνος (min) Τ1/2 = 210 min 3/2000 υπό θεραπεία /2001 υπό θεραπεία χρόνος (min) Τ1/2 = 200 min 2/2001 υπό θεραπεία χρόνος (min)

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49 GE Discovery 710 PET/CT - Τime of Flight (TOF) Γ Εργ. Πυρηνικής Ιατρικής ΑΠΘ, ΓΝ Παπαγεωργίου

50 128 PET/CT centers Americas (71%), Europe (22%), Asia-Pacific (6%), Middle East (1%) Public health care institutions (60%) Most frequent applications : torso or whole-body oncology (87%) neurology (5%) radiation therapy planning (4%) cardiology (4%) Beyer et al, JNMMI 2011

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53 analogues PET radiopharmaceuticals Carbohydrate 18F-FDG Aminoacids Positron emitter + Fatty acids Peptide Nucleotide Ligands Molecular imaging!

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55 FDG tumor model Glycolysis Normal cell FDG6P Glucose 6-phosphatase G6P Hexo kinase Glucose 6-phosphatase FDG G GLUTn FDG G Tumour cell Glucose 6-phosphatase FDG Hexo kinase G FDG6P G6P Glucose 6-phosphatase Glycol.

56 is this patient diabetic?

57 SUV : Standardized Uptake Value a t (Bq) SUV = V t (ml) A d (Bq) BW (kg)

58 SUV : tumor characterisation N, new disease R, recurrent disease Indolent Lymphoma grade 2 SUV 6.3 Aggressive lymphoma (relapsed large B-cell lymphoma) SUV 14.7 Schöder H et al. J Clin Oncol, 2005

59 SOURCES OF VARIABILITY - Tumor biology - Tumor heterogeneity - Body habitus - Blood Glucose levels - Variable uptake period - Tumor size (PVE) - Reconstruction parameters - ROI definition - CT AC settings SOURCES OF ERROR High SUV!!! Weber WA, JNM Paravenous injection - Residual syringe activity - No decay correction - Inaccurate cross-calibration of scanner or dose calibratoror

60 PET in diabetic patients Glu 200 mg% Glu 79 mg%

61 Diffuse bowel uptake of 18F-FDG on PET/CT examination of a patient with diabetes treated with metformin Bevilacqua T et al. BMJ Case Rep 2014

62 Impact of Medication Discontinuation on Increased Intestinal FDG Accumulation in Diabetic Patients Treated With Metformin Oh JR et al. AJR 2010

63 Impact of Medication Discontinuation on Increased Intestinal FDG Accumulation in Diabetic Patients Treated With Metformin Oh JR et al. AJR 2010

64 Impact of Medication Discontinuation on Increased Intestinal FDG Accumulation in Diabetic Patients Treated With Metformin Oh JR et al. AJR 2010

65 18F-FDG PET/CT scanning and diabetic patients: what to do? euglycaemia postprandial insulin acutely ID poorly controlled DM ID well-controlled DM metformin Martin MJ et al. NMC 2014

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