18F Radiopharmaceuticals :18F Radiopharmaceuticals Applications and Procedures Written and Presented By: Rotha Mam


Objectives :Objectives Briefly discuss the characteristics of 18F and 18F labeled products Discuss how 18F is used clinically Describe in detail the most commonly performed procedures involving the use of 18F Quickly summarize the applications and procedures involving 18F


18F and Positron Emission Tomography (PET) :18F and Positron Emission Tomography (PET) 18F is exclusively utilized in PET imaging. Flourine-18 is produced by irradiation of 18O-water with protons in a cyclotron and recovered as 18F-sodium fluoride by passing the irradiated water target mixture through a carbonate type anion exchange resin column.


18F Radiopharmaceuticals :18F Radiopharmaceuticals 18F-Sodium Fluoride FDA approved for bone scintigraphy 18F-Fluorodeoxyglucose (FDG) Used primarily for the study of metabolism in the brain and heart and for the detection of epilepsy and various tumors 18F-Flurodopa Assessment of the presynaptic dopaminergic function of the brain 18F-Fluorothymidine (FLT) Used for in vivo diagnosis and characterization of tumors in humans


18F-fluorodeoxyglucose (FDG) :18F-fluorodeoxyglucose (FDG) Most widely used radiopharmaceutical. Biochemically, 18F-FDG is a nonphysiological compound with a chemical structure very similar to that of naturally occurring glucose


Brain Imaging with 18F-FDG :Brain Imaging with 18F-FDG Indications Evaluation of presurgical refractory seizure disorders Localization of epileptic seizure focus in patients with intractable noncomplex seizure disorders. Detection of Alzheimer’s disease (AD) Differentiation between AD and frontotemporal dementia (FTD), and other dementia Differentiation between AD, normal aging, and neuropsychiatric conditions Evaluation of recurrent brain tumors Evaluation of stroke, extent and recovery following therapy.


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Patient Dose Range 10-20 mCi (370-740 MBq) Patient Preparation Have patient fast for 4 to 6 hours before procedure Monitor blood glucose levels before injection No caffeine, alcohol, or nicotine 24 hours prior to procedure Place patient in a quiet, darkened room at least 10 minutes before injection and 30 minutes after injection


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Relevant Questions Regarding Patient Information When was your last meal? Are you claustrophobic? Have you had any recent therapy or surgery? Have you had any caffeine, alcohol, or nicotine products in the last 24 hours? Has there been any recent memory loss? Is there a history of any brain disorders? Have there been any recent behavioral changes or confusion? Has there been any recent head trauma or headaches?


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Precautions Agitation or stress may affect the distribution of 18F-FDG Patient with severe claustrophobia may not be able to stay completely still during the procedure. Anti-anxiety medication may be indicated following physician approval Uncontrolled diabetes and/or blood sugar levels may lead to high serum glucose levels which hinder tumor uptake


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Method of Administration Intravenous butterfly or indwelling catheter Method of Localization Distributed according to regional cerebral blood flow. FDG is a substrate for the glucose transporter and hexokinase conversion to FDG-6-phosphate, but goes no further than that first step and is not metabolized causing “metabolic trapping” FDG does not undergo tubular reabsorption in the kidneys and is excreted in the urine.


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Acquisition Camera Large FOV gamma camera Dedicated PET camera PET/CT scanner Collimator Ultra-high energy, high resolution (gamma camera) None in 3D PET imaging Present in 2D PET imaging Computer Set-up Photopeak: 350-650 keV for BGO crystal, 435-665 keV for NaI crystal Attenuation correction can be done with cesium, germanium, or CT Images done in step-and-shoot protocol


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Processing Filter and reconstruct in transverse, coronal, and sagittal planes, according to manufacturer’s specifications. Images of head, neck and torso are to be reconstructed using “segmented attenuation correction” (SAC). Coronal and axial views, as well as additional views, can be printed out at the request of the reading physician.


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Interpretation Normal Results Highest uptake in gray matter or cortex, basal ganglia, and thalami. Symmetric and reasonably uniform Areas stimulated during injection of FDG will have a higher uptake Abnormal Results High uptake in ictal seizure focus Variable uptake in recurrent tumors Asymmetry or high uptake in certain lobes may indicate Dementia, Alzheimer’s, or Parkinson’s disease.


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) Sources of Error Patient stimulation during injection or procedure Insufficient fasting prior to procedure Interfering medication Patient movement during acquisition


Brain Imaging with 18F-FDG (cont.) :Brain Imaging with 18F-FDG (cont.) The PET examination demonstrates increased FDG activity corresponding to the generalized meningeal enhancement as well as to the focal thickening. These findings are also compatible with carcinomatosis. Note also the decreased metabolic activity in the left frontal lobe from the vasogenic edema.


Cardiac Perfusion and Viability :Cardiac Perfusion and Viability Indications Assessment of coronary artery disease (CAD) in symptomatic or asymptomatic patients Assessment of physiologic stenosis for revascularization Differentiation between viable tissue or necrotic tissue in patients with suspected hibernating or stunned myocardium Quantification of myocardial blood flow


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Patient Dose Range 10-15 mCi (370-555 MBq) Patient Preparation No caffeine, alcohol, or nicotine products within 24 hours of exam Patient is to eat light breakfast or lunch or is inject with glucose solution 1 to 3 hours before injection. Prepare patient with ECG setup if the study is gated. Patient should void immediately before imaging


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Relevant Questions Regarding Patient Information Are you diabetic? Do you have a history of heart attacks? Have you had any chest pain? Do you smoke? Are you using nitroglycerin? Do you take insulin? When did you eat last? Have you had any caffeine, alcohol, or nicotine products in the last 24 hours? Have you had any surguries within the last 6 months? Do you have a pacemaker? Have you had any recent chemo or radiation therapy?


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Precautions Patient is too agitated, medically compromised, or uncooperative to remain completely still. Patient has uncontrollable diabetes If performing a stress test, patient with severe asthma, brochospasms, COPD, unstable angina, recent myocardial infarction, hypotension, sick sinus syndrome, second and third degree AV block without pacemaker.


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Method of Administration Intravenous butterfly or indwelling catheter Veins in the foot may be preferred Any glucose or insulin loading should be done 80 to 120 minutes before FDG injection. Method of Localization FDG is a substrate for the glucose transporter and hexokinase conversion to FDG-6-phosphate, but goes no further than that first step and is not metabolized causing “metabolic trapping” FDG does not undergo tubular reabsorption in the kidneys and is excreted in the urine.


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Acquisition Dynamic: 18 frames at 10 sec/frame or 5 minutes as per protocol. Static: 6 to 15 minute image. Attenuation correction can be done with cesium, germanium or CT. Inject tracer, wait 70 seconds with patient at rest. Acquire dynamic rest emission scan. Transmission scan for attenuation correction (before or after emission, can take 10-20 minutes)


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Processing Reconstructed images should be reviewed for areas of attenuation Images can also be compared to a database of normal results Images should be displayed in their proper views such as short axis, vertical long axis, and horizontal long axis as seen in the next slide


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.)


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Interpretation Normal Results FDG uptake is uniform through most of the left ventricular myocardium with less uptake in the septum Globally synchronous if gated study Abnormal Results Focal areas of low uptake my indicate infarct or ischemia Right ventricular wall hypertrophy


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Sources of Error Patient who drank caffeine may have increased cardiac uptake Breast attenuation High-density barium from previous exams Metal objects not removed from patient Patient motion from discomfort of arm positioning. Arms down may necessitate longer imaging time False-positives can occur from misregistration between transmission and emission scans Patients with diabetes can seriously affect the interpretability of a scan


Cardiac Perfusion and Viability (cont.) :Cardiac Perfusion and Viability (cont.) Vertical long axis (A, B) and short axis (C, D) 18F-FDG-PET images of patient with myocardial infarction. Non-transmural defect at apex and anterior wall before surgical therapy (A, C). Three months after cell transplantation and CABG, anterior wall and apex showed increased viability (arrows) in infracted area (B, D).


Whole Body Tumor Imaging :Whole Body Tumor Imaging Indications Detection, localization, and staging of primary, metastatic, and/or recurrent tumors Differentiation between benign and malignant tumors Detection of unknown primary disease when malignancies are present Evaluation of elevated tumor markers or symptoms Evaluation of multiple myeloma Evaluation of oncologic therapies


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Patient Dose Range 4-20 mCi (148-740 MBq) Patient Preparation NPO at least 6 hours before exam No caffeine, alcohol, or nicotine products within 24 hours of exam Some procedures include monitoring the blood glucose levels before injection A laxative may be given the night before to reduce bowel activity


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Relevant Questions Regarding Patient Information When was your last meal? Have you had any recent sickness or infections? Have you had any vigorous exercise in the last 24 hours? Are you claustrophobic? Have you had any recent chemo or radiation therapy? Have you had any recent diagnostic procedures? Do you have a history or family history of cancer?


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Precautions High serum glucose levels will hinder tumor uptake FDG does not present well in all kinds of tumors Patient unable to stay still may be given anti-anxiety medication at physician’s approval Too much muscle activity before the examination Any other conditions that might hinder cellular metabolism of FDG


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Method of Administration Intravenous butterfly or indwelling catheter Injection should be administered in a site contralateral to area of interest Method of Localization FDG is a substrate for the glucose transporter and hexokinase conversion to FDG-6-phosphate, but goes no further than that first step and is not metabolized causing “metabolic trapping” FDG does not undergo tubular reabsorption in the kidneys and is excreted in the urine.


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Acquisition Image at 45 minutes after injection Photopeak: 300 to 650 keV for BGO crystal or 435-665 for NaI crystal Emission image: 6 to 15 minutes per bed position, collecting 5 to 15 million counts, depending on the area of interest. Transmission scan can be done either before or after emission scan FDG can be used in conjunction with 18F-sodium fluoride (bone imaging agent) to provide anatomical landmarks


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Processing Images are filtered and reconstructed into transverse, coronal, and sagittal planes A rotating maximum intensity projection (MIP) can be useful in detection and localization of tumors At authorized user’s request, PET studies can be fused with CT using software if scanner is not a fusion camera


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Interpretation Normal Results Uptake in brain, soft palate, tongue, vocal cords, palatine tonsils, adenoids, parotids, submandibular glands, thyroid, and neck muscle Low level uptake in lung, breast, testis and penis Increased uptake in surgical wounds No activity seen in pancreas, prostate, lymph nodes, or around breast implants Abnormal Results Uptake in neoplasms Increased uptake in infections and inflammatory type tissue High uptake in granulomas An SUV of greater than 2.5 is suggestive of malignancy


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Sources of Error Excessive physical activity Food intake Infection and inflammatory disease may give false positives Care should be taken during interpretation of a patient who has undergone chemotherapy and radiation which may decrease tumor uptake. Appearance of peripheral body or skin activity with reconstruction without attenuation correction


Whole Body Tumor Imaging (cont.) :Whole Body Tumor Imaging (cont.) Whole body tumor imaging indicates that findings are consistent with left upper lobe pulmonary malignancy with left hilar, mediastinal, right cervical and splenic metastases.


Conclusion :Conclusion PET imaging with 18F-FDG can be used for numerous applications Most common applications are in the areas of neurology, cardiology, and oncology Though FDG’s uses are broad, the procedures are similar in regards to patient preparation and precautionary measures


Question 1 :Question 1 What is the half-life of Flourine-18?


Answer 1 :Answer 1 Approximately 110 minutes


Question 2 :Question 2 What is the primary mode of decay and it corresponding percentage?


Answer 2 :Answer 2 Positron decay; 97%


Question 3 :Question 3 What is the maximum energy (Emax) of Flourine-18?


Answer 3 :Answer 3 635 keV


Question 4 :Question 4 What is the most widely used radiopharmaceutical used in PET imaging and what physiological compound does it mimic?


Answer 4 :Answer 4 18F-FDG; glucose


Question 5 :Question 5 Name one indication for brain imaging with FDG.


Answer 5 :Answer 5 Evaluation of presurgical refractory seizure disorders Localization of epileptic seizure focus in patients with intractable noncomplex seizure disorders. Detection of Alzheimer’s disease (AD) Differentiation between AD and frontotemporal dementia (FTD), and other dementia Differentiation between AD, normal aging, and neuropsychiatric conditions Evaluation of recurrent brain tumors Evaluation of stroke, extent and recovery following therapy.


Question 6 :Question 6 Name one indication for a cardiac perfusion study using FDG.


Answer 6 :Answer 6 Assessment of coronary artery disease (CAD) in symptomatic or asymptomatic patients Assessment of physiologic stenosis for revascularization Differentiation between viable tissue or necrotic tissue in patients with suspected hibernating or stunned myocardium Quantification of myocardial blood flow


Question 7 :Question 7 Name one indication for a whole body tumor scan using FDG.


Answer 7 :Answer 7 Detection, localization, and staging of primary, metastatic, and/or recurrent tumors Differentiation between benign and malignant tumors Detection of unknown primary disease when malignancies are present Evaluation of elevated tumor markers or symptoms Evaluation of multiple myeloma Evaluation of oncologic therapies


Question 8 :Question 8 How is FDG localized?


Answer 8 :Answer 8 FDG is taken into the cells in the same fashion as glucose, but is not metabolized causing “metabolic trapping”


Question 9 :Question 9 How is FDG removed from the body?


Answer 9 :Answer 9 It is excreted in urine


Question 10 :Question 10 Since FDG is concerned with glucose metabolism, what are some concerns when preparing a patient?


Answer 10 :Answer 10 Whether the patient is diabetic and if he/she has eaten prior to the exam


References :References Shackett P. (2009) Nuclear Medicine Technology: Procedures and quick reference. Wolters Kluwer (196-229_ Christian P. (Ed.). (2007) Nuclear Medicine and PET/CT. Rochestor (368-394) http://www.radiologyinfo.org/en/info.cfm?pg=PET&bhcp=1