Jiraporn Sriprapaporn, M.D.Nuclear medicine
Siriraj Hospital
The Society of Medical Radiography of Thailand Meeting, Pattaya, Thailand5 July 2012
TopicsTopics
• What is PET?• Evolution of PET/CT• Principle of PET/CT imaging
– PET/CT scanners– PET radiopharmaceuticals
• Steps of PET/CT imaging• Oncologic applications of PET/CT
What is PETWhat is PET??
Nuclear Medicine StudiesNuclear Medicine Studies
Gamma Camera
SPECT
PET
2-D Images
3-D Images
3-D Images
What is PETWhat is PET??
• PET: Positron emission tomography• PET is the study of human physiology by
electronic detection of short-lived positron emitting radiopharmaceuticals.
• PET is used to evaluate metabolic,biochemical and functional activity at cellular level of human living.
Historical PerspectivesHistorical Perspectives of PET Scanof PET Scan
• The first CT scanner was invented in 1972 by British engineer Godfrey Hounsfield & Allan Cormack (later awarded the Nobel Peace Prize)
• The first PET camera was built for humanstudies by Edward Hoffman, Michael M. Ter-Pogossian, and Michael E. Phelps in 1973 at Washington University.
• The first whole-body PET scanner appeared in 1977.
• 1980The first commercial MRI scanner was produced by Raymond Damadian and Paul Lauterbur.
1972
1973
1977
1980
• The PET/CT scanner was invented by Dr. Ron Nutt and Dr. David Townsend in 1998
• Medical Inventions of the year 2000 by Time Magazine
• 2001commercially available
PET Scan ImagesPET Scan Images
COLD WARM
PET alone lacks of detailed anatomy
BROWN FATBROWN FAT
http://www.nuclearonline.org/Newsletter/CaseStudy905.htm
Integrated
PET-CT Scan
PETPET--ONLY VS PETONLY VS PET--CTCT
• Longer scanning time
• Lower patient throughput
• Limited anatomical information
• Shorter scanning time.
• Increase patient throughput
• Better anatomical details– Improve diagnostic
accuracy
• Can combine contrast CT study
PETPET--CT ImagingCT Imaging
PET/CT Scanner
Patient PET Radiopharmaceutical
PETPET--CT CT ScannersScanners
CT PET
PET RadionuclidesPET Radionuclides
• Positron-emitting radionuclides (emit positron (e+) from nucleus (p excess)
• Relatively short half-lives and high radiation energies (compared to general NM imaging)
• Produced by cyclotron or generators
CYCLOTRONCYCLOTRON
Important Important PositronPositron EEmittmittersers
Positron Emitters
• C-11• N-13• O-15• F-18
Physical T1/2
• 20 min• 10 min• 2 min• 110 min
PEPET RadiopharmaceuticalsT Radiopharmaceuticals
• F-18 FDG is the most commonly used PET tracer.
• F-18 FDG (18F-2-fluoro-2-deoxy-D-glucose) or fluorodeoxyglucose (glucose analogue)
• Glucose metabolism
Steps Steps of of PETPET//CTCTImagingImaging
• Production of positron-emitting Rdn.
• Labeling a selected compound with a positron-emitting Rdn.
• Administration into a patient (IV, inhalation)
• PET/CT Imaging the patient• Reconstruction & display
(Quantitation)
CYCLOTRON
COMPUTER
PET-CT SCANNER
RADIOPHARM PREP.
INJ. PATIENT
PET IMAGING
PETPET--CT ImagingCT ImagingCT PETPET/CT ImagingPET/CT Imaging
• Scout CT• CT low mA• PET scan-Non AC• PET-AC• PET(AC)/CT
Display of PETDisplay of PET--CT ImagesCT Images
MIP
MIP: Maximum Intensity Projection
Combined functional
&anatomical information
PET ImagingPET Imaging
• Detecting (indirectly)positron emission via the detection of both annihilation photons(511 keV) that occur and hit opposite detectors simultaneously
• Spatial resolution ~4-5 mm FWHM
e-
e+
annih
Nu
PET Detector PET Detector
PET AnnihilationPET Annihilation
PETPET--CT CT Clinical ApplicationsClinical Applications
The Lifetime Risk The Lifetime Risk of Cancerof Cancer
• SEER Cancer Statistics Review, 1975-2009(http://www.cancer.org/Cancer/CancerBasics/lifetime-probability-of-developing-or-dying-from-cancer)
• Great Britain, 1975-2008(http://info.cancerresearchuk.org/cancerstats/incidence/risk/statistics-on-the-risk-of-developing-cancer)
> 1/3 risk to have cancer in their lifetime
M 45%
F 38%
M 42%
F 39%
4 Factors Facilitate Widespread Use of FDG 4 Factors Facilitate Widespread Use of FDG PET/CT ImagingPET/CT Imaging
1. Whole-body scanning; great impact for the detection of distant metastatic sites in cancer patients.
2. Availability of 18F FDG for hospitals that do not have a cyclotron
3. Combined PET and CT images in a single setting (PET/CT)
4. The approval of reimbursement for PET/CT using F-18 FDG for most oncologic studies.
Endo K et al. 2006
Limitation of using PET/CT in Limitation of using PET/CT in ThailandThailand
• Limited availability
• Very high cost (higher than MRI)
• Very limited reimbursement– Lung cancer: staging NSCLC (prior surgery)– Colorectal cancer: Suspected tumor recurrence
Appropriate uses cost-effective
1818FF--FDG PETFDG PET//CT ImagingCT Imaging in Oncologyin OncologyAdvantages DisadvantagesAdvantages Disadvantages
• Several tumors
• Whole-body imaging distant metastasis
• Function & anatomy
• High resolution (PET technique)
• High sensitivity (depends on metabolic activity)
• High accuracy (due to combined CT images)
• Good patient tolerance
– about 30 min, no noise
• Nonspecific for tumor types
• Can be false positive for infection-inflammation.
• May be low sen & spec in very small lesions (<0.5 cm)
• Radiation (low-dose CT scan & PET)
• Image artifacts can occur with CT, contrast.
Mechanism of Tumor UptakeMechanism of Tumor Uptake
• Malignant cells have increased glucose utilization.
• Once in the tumor cells, FDG is converted intoFDG-6-phosphate, which is metabolically trappedin the tumor cells.
• Thus, PET scan show increased FDG uptake in the tumors.
FDG MetabolismFDG Metabolism
Enz1 = Hexokinase -- Phosphorylation
Enz2= Glucose-6-phosphatase
Tumor cells higher glycolytic rate than normal tissue.
1
1
2
2
Glycolysis
• PET= metabolic imaging• FDG (flourodeoxyglucose) is a glucose
analog.• F-18 FDG is the most commonly used
PET tracer for oncology.• Mech: Active transport into cells, once
intracellular FDG is phosphorylated by hexokinase but FDG cannot enter glycolysis and becomes metabolically trapped in the cells as FDG-6-Phosphate
• Tumors increased metabolic activity- increased glycolysis increased FDG uptake
Normal Normal FF--18 18 FDG DistributionFDG Distribution
• Brain• Heart
(postprandial*)• Liver• Kidneys-BL• Muscle
• GI tract• Bone marrow• Lymphoid-thymus• Breast• Gonad• Vascular activity
RRadiation exposure from PETadiation exposure from PET//CT imaging CT imaging
• Results: Effective dose from whole-body CT is about 18 mSv, comparable to that for a typical diagnostic abdomen and pelvis CT series.
• When adding the effective dose from F-18 FDG of about 7 mSv, the effective dose from a PET/CT study is about 25 mSv.
• Conclusions:– The effective doses from WB PET/CT studies are
similar to that from a diagnostic abdomen andpelvic CT, respectively.
– Patients acquiring 2 PET/CT exams a year will receive an equivalent whole-body x-ray dose equal to the 50 mSv annual maximum permissible dose for occupational radiation workers.
Vicki Quan et al.Vicki Quan et al. JNMJNM 20072007
FDG ImagingFDG Imaging:: TechniquesTechniques
• Fasting at least 4-6 hours prior to FDG-PET study.– FBS 70-110 ng/dl is ideal for FDG-PET
• IV. inject 140uCi/Kg of FDG (10-20 mCi)• 45-60 minutes following iv. FDG, PET scan is performed.• Skull base-to-mid-thighs or head-to-toe• PET scan time: 2-3 min/ bed position• CT scan: low mA scan is adequate for attenuation
correaction & anatomical localization.• High mA scan is needed for diagnostic CT scan.• Oral contrast and IV contrast (diagnostic CT)
SUV SUV (Standardized Uptake Value)(Standardized Uptake Value)
• Semi-quantitative measurement of degree of FDG accumulation in the ROI to the total injected dose and the patient's BW. [R41. Lowe VJ, Naunheim KS. Thorax 1998]
• Malignant tumors: increased glycolytic rate
Concentration in ROI SUV = ---------------------------------------
Injected Dose / BW
Clinical Applications of FClinical Applications of F--18 FDG 18 FDG
in in
Oncologic PatientsOncologic Patients
Jiraporn SriprapapornFaculty of Medicine, Siriraj Hospital
Oncologic Indications for 18FOncologic Indications for 18F--FDG PET/CTFDG PET/CT
• Differentiating benign from malignant lesions • Searching for an unknown primary tumor • Staging known malignancies • Monitoring the effect of therapy on known
malignancies• Determining whether residual tumor or
posttreatment fibrosis or necrosis • Detecting tumor recurrence, especially in the
presence of elevated levels of tumor markers • Selecting the region for tumor biopsy • Guiding radiation therapy planning
Delbeke D et al. JNM 2006
PET in Oncology: PET in Oncology: Common Applications Common Applications
1. Single pulmonary nodule (SPN)2. Lung cancer (NSCLC*)3. Colorectal cancer*4. Lymphoma5. Melanoma6. Esophageal cancer7. Head & neck cancer8. Thyroid cancer9. Breast cancer10. Cervical cancer
* Reimbursed by Thai government // rules
Solitary Pulmonary NoduleSolitary Pulmonary Nodule
• DxCT: – Primary tumor-Rt– Med node –ve
• PET-CT (12-06): – Hypermetabolic,
SUVmax = 8Malignant nodule !
– Med node –ve– Distant met-No
PET for NPET for N--Staging of NSCLCStaging of NSCLC
• CT: Left NSCLC w a pathologic AP window node (N2) (white),and a non-pathologic retrocaval-pretracheal contralateral mediastinal node (N3) (yellow).
• PET-FDG images: increased tracer accumulation within both nodes, consistent with metastases.
• Thus, PET is more sensitive than CT in detect small hypermetabolic LN metas.
www.auntminnie.com
VK 30VK 30--55--20122012
• A 69-year-old male with history lung cancer at RUL (adenocarcinoma)with liver and subcutaneous metastases s/p CMT last 30-3-2012.
• PET/CT imaging (30-5-2012)demonstrated widespread metastases: liver, subcutaneous, bone, adrenal, pancreas, soft tissue, peritoneum.
• Mild hypermetabolic thyroid nodule.
MIP
Adrenal metastasis
Liver metastasis
Axial PET/ CT Scan_Abdomen
30-5-2012
Axial PET/ CT Scan_Chest
Rt. Scapular metastasis
30-5-2012
Sagittal PET/ CT Scan_Spine metastatses
30-5-2012
WB PET Scan_Coronal (BW) 30-5-2012
CS 2012CS 2012
• History: 30-yo male with diffuse large B-cell lymphoma Dx in March 2012, presenting with SVC obstruction.
• PET/CT Findings:– 1st study-staging preRx (5-4-12)
• Huge hypermetabolic tumor at anterior mediastinum. (SUVmax 18.8)
– 2nd study-post CMT (5-6-12)• Marked reduction of tumor size at ant mediastinum
with metabolic response. (SUVmax 6.8)
5-4-12 5-6-12
Lymphoma: Pre & Post TreatmentLymphoma: Pre & Post Treatment
Pre-treatment 5-4-2012
Post-treatment 5-6-2012
Colorectal CA w Liver Metas.: Colorectal CA w Liver Metas.: prepre--post Rxpost Rx
• Figure 4 Patient with colorectal metastases and previous left hemihepatectomy.
• A CT shows two hypodense nodules with contrast enhancement.
• B PET/CT fusion indicates a metastatic recurrent tumor beside a scar after operation.
• C CT after radiofrequency ablation shows a large area without contrast enhancement (arrow).
• D PET/CT fusion after radiofrequency ablationindicates complete ablation of the recurrent metastasis with a photopenic lesion.
Colorectal CA w Liver MetasColorectal CA w Liver Metas--: : Tumor RecurrenceTumor Recurrence
Figure 5• A CT 3 month after radiofrequency ablation shows
no sign of local recurrence.• B PET/CT 3 month after radiofrequency ablation
demonstrates a local recurrent tumor.
A 62A 62--yearyear--old man with papillary old man with papillary thyroid carcinomathyroid carcinoma
• s/p total thyroidectomy and cervical node dissection on 11-3-07 and resurgery on 14-7-10 and 3 doses of RAI Rx last on 21-9-10.
• Post-therapeutic I-131 TBS on 24-9-10 was negative, while Tg was 662.2 ng/ml.
II--131 TBS vs F131 TBS vs F--18 FDG PET18 FDG PET
Anterior Posterior MIP Coronal PET
PET/CT Scan PET/CT Scan (9(9--1111--2010)2010)
• Large hypermeta-bolic soft tissue mass at left side of neck, measured 8.5x3.7x1.9 cm. Recurrent thyroid cancerERT, RFATg from 662 2.1 ng/ml on 18-6-12.
• A 56-year-old female patient with papillary thyroid carcinoma since 1994 presented in 2002 with a Rt neck mass and rising Tg.
• 123I imaging (A) showed left hilar uptake posteriorly but no uptake in the neck.
• 18F-FDG PET scan (B) showed multiple metastatic lesions in the neck.
• 131I therapy was given and improved her mediastinal disease but there was no uptake in the neck metastases, which were removed surgically.
II--123 F18123 F18--FDGFDG
• A 63-year-old woman with follicular thyroid cancer.• I-123 WB scan is negative.• F-18 FDG PET-CT shows multiple pulmonary and
mediastinal lymph node metastases.
I-123 WBS F-18 FDG PET-CT
Lin FI 2010
• (A) A 27-year-old man had a total thyroidectomy and left-sided neck dissection for papillary thyroid carcinoma.
• A few years later he presented with an abnormally increased thyroglobulin level, but negative WB planar imaging I-131 (image a) and Tc-99m MDP bone scan (image b)
• (B) 18F-FDG-PET/CT revealed FDG-avid recurrent disease within the thyroidsurgical bed (red arrows), metastatic FDG-avid left supraclavicular node(blue arrow) and bony metastases within the upper thoracic vertebrae(green arrows)
Chua S SNM Nov 2009
Thyroid bed
SPC
T spine
Incidentally found right thyroid noduleIncidentally found right thyroid nodule
• 55-yo woman with a history of treated lymphoma was sent for surveillance PET/CT imaging.
• Hypermetabolic Rt thyroid nodule was incidentally found and proved to be papillary thyroid carcinoma.
Sriprapaporn J. Siriraj Med J 2011;63: 207-209
FF--18 FDG PET/CT Oncologic 18 FDG PET/CT Oncologic Applications Applications
1. Single pulmonary nodule (SPN)2. Lung cancer (NSCLC*)3. Colorectal cancer*4. Lymphoma5. Malignant melanoma6. Esophageal cancer7. Head & neck cancer8. Thyroid cancer9. Breast cancer10. Cervical cancer
* Reimbursed by Thai government // rules
Oncologic Indications for 18FOncologic Indications for 18F--FDG PET/CTFDG PET/CT
• Differentiating benign from malignant lesions • Searching for an unknown primary tumor • Staging known malignancies • Monitoring the effect of therapy on known
malignancies• Determining whether residual tumor or
posttreatment fibrosis or necrosis • Detecting tumor recurrence, especially in the
presence of elevated levels of tumor markers • Selecting the region for tumor biopsy • Guiding radiation therapy planning
Delbeke D et al. JNM 2006
FDGFDG--PET PET -- False NegativeFalse Negative
• Small lesions < 10 mm, not much active• Hyperglycemia, diabetes• High background neoplastic process
– Brain tumors, RCC, soft tissue sarcoma • Low grade malignancies
– Low grade lymphoma, well-diff DTC– Bronchoalveolar CA and bronchial carcinoid
• Tumors high in G-6-phosphatase eg. HCC • Tumors with large amounts of mucin
FDGFDG--PET PET -- False PositiveFalse Positive
• FDG is not a cancer-specific agent. !– Infection/Inflammatory lesions
• Post-surgical, healing wound, post RT• Sarcoidosis, TB• Abscess, fungal infection• etc.
Better to interpret PET and CT scan images together with clinical information to enhance the specificity
ConclusionConclusion
• Due to presence of FP & FN results, it’s better to interpret PET and CT scan images together with clinical information to enhance the interpretation accuracy.
PET + CT + CLINICAL INFO