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

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"

5. What is Insulin?

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

10. Elevated BSL

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

12. Elevated Insulin levels

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

25. Diagnostic scan with 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?