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