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So you’re a diabetic!

The role of blood sugar levels and
          insulin in PET
Overview
•   What is BSL?
•   What is Insulin and how it works?
•   Diabetes in Australia
•   Role of diabetes and PET
•   Patient Instructions
•   Guidelines for diabetes and PET
•   Difficulties of diabetes and PET
What is “blood sugar level”?
• Amount of glucose in blood
• Glucose is the primary source of energy for cells
• Normal range between 3.9-6 mmol/L
• Between 3.3-7g (assuming and ordinary blood
  volume of 5lt)
• Other sugars such as Fructose and Galactose
  are found in blood
• Only Glucose is regulated by Insulin
What is Insulin?
• Peptide hormone composed of 51 amino acid
  residues
• Produced in the Islets of Langerhans in the
  pancreas
• Causes most of the body's cells to take up
  glucose from the blood (including liver, muscle
  and fat tissue cells), storing it as glycogen in the
  liver and muscle
• Latin insula for "island"
What is Insulin?
How does Insulin work?




• Effect of insulin on glucose uptake and metabolism. Insulin
  binds to its receptor (1) which in turn starts many protein activation
  cascades (2). These include: translocation of Glut-4 transporter to
  the plasma membrane and influx of glucose (3), glycogen synthesis
  (4), glycolysis (5) and fatty acid synthesis (6).
Types of Diabetes
• Type 1
  –   Auto-immune disease
  –   Depend on external insulin
  –   Insulin is no longer produced internally
  –   Insulin depletion is virtually complete
  –   4-5 injections daily

• Type 2
  –   Accounts for 85% of diabetes
  –   Insulin resistant
  –   Have relatively low insulin production
  –   Or both
Diabetes in Australia
• Fastest growing epidemic in human history
• 275 Australians become diabetic every
  day
• 2 million Australians diabetic by 2020
• One death every 10 seconds globally
Why is BSL an issue in PET?

• Ensure that serum glucose levels are low
  at the time of FDG administration
• Glucose competes with FDG for cellular
  uptake
• Sustained blood pool tracer activity
• Some evidence that elevated BSL lowers
  uptake in malignant neoplasms
Elevated BSL
Why is Insulin an issue in PET?
• Elevated serum insulin promotes FDG
  uptake in liver and muscle
• Insulin induced hypoglycaemia can impair
  tumour uptake
Elevated Insulin levels
Patient Instructions for Diabetics
• No standard protocol
• Doctor dependant
• Consultation with patients
  –   No insulin
  –   Half insulin
  –   Later booking
  –   Light meal
  –   Full meal
  –   ?
Patient Instruction for Diabetics
• Contacted 6 major PET sites in Australia
  and Switzerland
  – Royal Brisbane, Qld
  – Sir Charles Gardiner, WA
  – Westmead, NSW
  – Liverpool, NSW
  – Austin, Vic
  – University Hospital, Basel, Switzerland
Westmead
• Stable Diabetics
  – Fast 4hrs and have all medications
• Unstable Diabetics
  –   Early afternoon appointment
  –   Normal breakfast
  –   Normal medications
  –   Arrive at 10am to walk/hydrate patient to get BSL
      down
• Only inject if BSL <8
• Never inject insulin
Liverpool
• Diet Controlled & Non-insulin dependant
  – Fast 6 hrs
  – Normal medications
• Insulin Dependant
  – Fast 4hrs
  – Normal medications
• Only inject if BSL <10
• Never inject insulin
Austin
• All diabetics
  – Fast 4 hrs
  – Take full medications
• If BSL is higher than patients “normal”
  range then reschedule
• Rarely inject insulin
• Longer uptake time 75-90mins!
University Hospital
• All diabetics
  – Fast 6hrs
  – Take all medications
• If BSL >12 inject insulin, wait 1-2hrs
  before FDG injection
Overview of patient instructions
         Fasting Insulin Wait time   Acceptable
         Period                         bsl
Westmead 4hrs      No     60mins      8mmol

Liverpool   4hrs    No      60mins   10mmols

 Austin     4hrs   Rarely     75-      Varies
                            90mins
  Basel     6hrs    Yes       90        All

   Us       6hrs   Rarely   60mins       ?
SNM Procedure Guidelines
• Procedure Guideline for Tumor Imaging Using F-18 FDG
  v2.0, Feb, 1999
   – Fast 4hrs
   – No mention of insulin
• Procedure Guideline for Tumor Imaging with18F-FDG
  PET/CT v1.0, May, 2006
   – Fast 4-6hrs
   – “most institutions reschedule if BSL is <150-200mg/dL” 8.3mmol
     to 11.1mmol
   – “reducing the serum glucose level by administering insulin can
     be considered, but the administration of FDG should be delayed
     with the duration of the delay being dependent on the type and
     route of administration of insulin.”
EANM Procedure Guidelines
• FDG-PET Procedure Guidelines for Tumour
  Imaging v1.0 Sept, 2003
  – Fast 6hrs
  – Study not recommended when the glucose level in
    the blood exceeds 200 mg/dl. (11.1 mmol)
  – There are no general guidelines for FDG-PET in
    cancer diagnosis in diabetic patients.
  – Many centres have the patients fast and do not
    administer additional insulin despite the presence of
    hyperglycaemia, and obtain useful diagnostic images
  – No other mention of insulin
Overview with guidelines
            Fasting Insulin Wait time   Acceptable
            Period                         bsl
Westmead     4hrs     No     60mins      8mmol
Liverpool    4hrs    No      60mins     10mmols
 Austin      4hrs   Rarely     75-       Varies
                             90mins
 Basel       6hrs  Yes         90           All
   Us        6hrs Rarely     60mins         ?
  SNM       4-6hrs  ?        60mins      8.3-11.1
 EANM        6hrs   ?        60mins        11.1
How many diabetics with
     elevated BSL do we do?

• Oct 2004 – May 2008
• 2896 scans
• > 150mg/dcl (8.3mmol)
  – 125 patients, 4.3%
• > 200mg/dcl (11.1mmol)
  – 41 patients, 1.4%
Should we inject Insulin?
• Subcutaneous regular insulin is released
  progressively over a period that typically
  exceeds four hours.
• Insulin has its maximum effect between 15
  and 45 minutes p.i.
• Common practice is to wait 4hrs before
  FDG injection following insulin
Diagnostic scan with Insulin
Delayed FDG inj following insulin
Insulin and FDG injection
•   Turcotte et al, Molecular Imaging and Biology, Oct 2006 Optimization of
    Whole-Body Positron Emission Tomography Imaging by Using Delayed 2-
    Deoxy-2-[F-18]fluoro-d -glucose Injection Following I.V. Insulin in Diabetic
    Patients
     – assess whether (i.v.) insulin followed by FDG injection
       60 minutes later could decrease the blood glucose
       level of hyperglycemic patients without altering
       muscular, liver, or lung FDG uptake
     – 53 diabetic patients with BSL >7mmol, 53 pts control
     – with a sufficient waiting period between the insulin
       and FDG injections, an i.v. bolus of insulin makes it
       possible to effectively decrease glyceamia of diabetic
       patients without increasing muscular FDG uptake
     – more than 90% of intravenous insulin cleared from
       the plasma by 20 minutes and 95% by 60 minutes.
Does diabetes affect SUV?
• BSL changes over uptake and scanning
  period
•   Gorenberg et al European journal of nuclear medicine and molecular
    imaging vol. 29, no10, pp. 1324-1327 Does diabetes affect [18F]FDG
    standardised uptake values in lung cancer?


     Regardless of glucose levels, DM and IDDM do not
      influence pre-treatment SUV scores in patients
Conclusion
• The role of blood sugar levels and insulin
  in PET is a complex issue
• Wide variations between PET centres
• No clear guidelines from professional
  bodies
• Do we need standardised guidelines or is
  case by case the best method?

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The role of blood sugar levels and insulin in pet

  • 1. So you’re a diabetic! The role of blood sugar levels and insulin in PET
  • 2. Overview • What is BSL? • What is Insulin and how it works? • Diabetes in Australia • Role of diabetes and PET • Patient Instructions • Guidelines for diabetes and PET • Difficulties of diabetes and PET
  • 3. What is “blood sugar level”? • Amount of glucose in blood • Glucose is the primary source of energy for cells • Normal range between 3.9-6 mmol/L • Between 3.3-7g (assuming and ordinary blood volume of 5lt) • Other sugars such as Fructose and Galactose are found in blood • Only Glucose is regulated by Insulin
  • 4. What is Insulin? • Peptide hormone composed of 51 amino acid residues • Produced in the Islets of Langerhans in the pancreas • Causes most of the body's cells to take up glucose from the blood (including liver, muscle and fat tissue cells), storing it as glycogen in the liver and muscle • Latin insula for "island"
  • 6. How does Insulin work? • Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).
  • 7. Types of Diabetes • Type 1 – Auto-immune disease – Depend on external insulin – Insulin is no longer produced internally – Insulin depletion is virtually complete – 4-5 injections daily • Type 2 – Accounts for 85% of diabetes – Insulin resistant – Have relatively low insulin production – Or both
  • 8. Diabetes in Australia • Fastest growing epidemic in human history • 275 Australians become diabetic every day • 2 million Australians diabetic by 2020 • One death every 10 seconds globally
  • 9. Why is BSL an issue in PET? • Ensure that serum glucose levels are low at the time of FDG administration • Glucose competes with FDG for cellular uptake • Sustained blood pool tracer activity • Some evidence that elevated BSL lowers uptake in malignant neoplasms
  • 11. Why is Insulin an issue in PET? • Elevated serum insulin promotes FDG uptake in liver and muscle • Insulin induced hypoglycaemia can impair tumour uptake
  • 13. Patient Instructions for Diabetics • No standard protocol • Doctor dependant • Consultation with patients – No insulin – Half insulin – Later booking – Light meal – Full meal – ?
  • 14. Patient Instruction for Diabetics • Contacted 6 major PET sites in Australia and Switzerland – Royal Brisbane, Qld – Sir Charles Gardiner, WA – Westmead, NSW – Liverpool, NSW – Austin, Vic – University Hospital, Basel, Switzerland
  • 15. Westmead • Stable Diabetics – Fast 4hrs and have all medications • Unstable Diabetics – Early afternoon appointment – Normal breakfast – Normal medications – Arrive at 10am to walk/hydrate patient to get BSL down • Only inject if BSL <8 • Never inject insulin
  • 16. Liverpool • Diet Controlled & Non-insulin dependant – Fast 6 hrs – Normal medications • Insulin Dependant – Fast 4hrs – Normal medications • Only inject if BSL <10 • Never inject insulin
  • 17. Austin • All diabetics – Fast 4 hrs – Take full medications • If BSL is higher than patients “normal” range then reschedule • Rarely inject insulin • Longer uptake time 75-90mins!
  • 18. University Hospital • All diabetics – Fast 6hrs – Take all medications • If BSL >12 inject insulin, wait 1-2hrs before FDG injection
  • 19. Overview of patient instructions Fasting Insulin Wait time Acceptable Period bsl Westmead 4hrs No 60mins 8mmol Liverpool 4hrs No 60mins 10mmols Austin 4hrs Rarely 75- Varies 90mins Basel 6hrs Yes 90 All Us 6hrs Rarely 60mins ?
  • 20. SNM Procedure Guidelines • Procedure Guideline for Tumor Imaging Using F-18 FDG v2.0, Feb, 1999 – Fast 4hrs – No mention of insulin • Procedure Guideline for Tumor Imaging with18F-FDG PET/CT v1.0, May, 2006 – Fast 4-6hrs – “most institutions reschedule if BSL is <150-200mg/dL” 8.3mmol to 11.1mmol – “reducing the serum glucose level by administering insulin can be considered, but the administration of FDG should be delayed with the duration of the delay being dependent on the type and route of administration of insulin.”
  • 21. EANM Procedure Guidelines • FDG-PET Procedure Guidelines for Tumour Imaging v1.0 Sept, 2003 – Fast 6hrs – Study not recommended when the glucose level in the blood exceeds 200 mg/dl. (11.1 mmol) – There are no general guidelines for FDG-PET in cancer diagnosis in diabetic patients. – Many centres have the patients fast and do not administer additional insulin despite the presence of hyperglycaemia, and obtain useful diagnostic images – No other mention of insulin
  • 22. Overview with guidelines Fasting Insulin Wait time Acceptable Period bsl Westmead 4hrs No 60mins 8mmol Liverpool 4hrs No 60mins 10mmols Austin 4hrs Rarely 75- Varies 90mins Basel 6hrs Yes 90 All Us 6hrs Rarely 60mins ? SNM 4-6hrs ? 60mins 8.3-11.1 EANM 6hrs ? 60mins 11.1
  • 23. How many diabetics with elevated BSL do we do? • Oct 2004 – May 2008 • 2896 scans • > 150mg/dcl (8.3mmol) – 125 patients, 4.3% • > 200mg/dcl (11.1mmol) – 41 patients, 1.4%
  • 24. Should we inject Insulin? • Subcutaneous regular insulin is released progressively over a period that typically exceeds four hours. • Insulin has its maximum effect between 15 and 45 minutes p.i. • Common practice is to wait 4hrs before FDG injection following insulin
  • 26. Delayed FDG inj following insulin
  • 27. Insulin and FDG injection • Turcotte et al, Molecular Imaging and Biology, Oct 2006 Optimization of Whole-Body Positron Emission Tomography Imaging by Using Delayed 2- Deoxy-2-[F-18]fluoro-d -glucose Injection Following I.V. Insulin in Diabetic Patients – assess whether (i.v.) insulin followed by FDG injection 60 minutes later could decrease the blood glucose level of hyperglycemic patients without altering muscular, liver, or lung FDG uptake – 53 diabetic patients with BSL >7mmol, 53 pts control – with a sufficient waiting period between the insulin and FDG injections, an i.v. bolus of insulin makes it possible to effectively decrease glyceamia of diabetic patients without increasing muscular FDG uptake – more than 90% of intravenous insulin cleared from the plasma by 20 minutes and 95% by 60 minutes.
  • 28. Does diabetes affect SUV? • BSL changes over uptake and scanning period • Gorenberg et al European journal of nuclear medicine and molecular imaging vol. 29, no10, pp. 1324-1327 Does diabetes affect [18F]FDG standardised uptake values in lung cancer? Regardless of glucose levels, DM and IDDM do not influence pre-treatment SUV scores in patients
  • 29. Conclusion • The role of blood sugar levels and insulin in PET is a complex issue • Wide variations between PET centres • No clear guidelines from professional bodies • Do we need standardised guidelines or is case by case the best method?