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 Period

Insulin Wait time Acceptable bsl

Westmead 4hrs No 60mins 8mmol

Liverpool 4hrs No 60mins 10mmols

Austin 4hrs Rarely 75-90mins

Varies

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 Period

Insulin Wait time Acceptable bsl

Westmead 4hrs No 60mins 8mmol

Liverpool 4hrs No 60mins 10mmols Austin 4hrs Rarely 75-

90mins Varies

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?