Integrated FDG-PET and PET/CT - Society of Nuclear Medicine

Integrated FDG-PET and PET/CT: Clinical Applications and Impact on Patient Care Dominique Delbeke, MD, PhD Vanderbilt University Medical Center Nashville, TN

Quanta, Curitiba, Brazil Mayo 26th, 2009

Positrons Emitters ƒ Produced in a cyclotron ƒ ƒ ƒ ƒ ƒ ƒ

Fluorine-18 (T1/2 = 110 min) Nitrogen-13 (T1/2 = 10 min) Carbon-11 (T1/2 = 20 min) Oxygen-15 (T1/2 = 2 min) Copper-64 (T1/2 – 12 h) Iodine-124 (T1/2 = 4 days)

ƒ Produced by generator ƒ ƒ ƒ

Rubidium-82 (T1/2 = 78 sec) Gallium-68 (T1/2 = 68 min) Copper-62 (T1/2 = 10 min)

RDS-111 PET Cyclotron (CTI, Knoxville, TN)

Assessment of Tumor Biology with PET ƒ PET assesses physiology and biochemistry rather than anatomy ƒ Therefore PET provides the potential for earlier, more sensitive detection of disease

PET Tracers of Perfusion ƒ Tracers of Perfusion ƒ 15O-water (cyclotron, T1/2 = 2 min) ƒ 13N-ammonia (cyclotron, T1/2 = 10 min) ƒ 82Rubidium (generator expensive! T1/2 = 78 sec)

Assessment of Tumor Biology with PET ƒ Perfusion ƒ Metabolism ƒ Glucose metabolism: 18F-fluorodeoxyglucose = FDG ƒ Bone metabolism: 18F-fluoride ƒ Membrane lipid synthesis:11C-acetate (i.e. HCC), 18F-choline ƒ Amino acid transport and metabolism: 11C-methionine , 18Ftyrosine

ƒ Cellular proliferation: 18F-fluorothymidine (FLT) ƒ Receptor expression: ƒ Estrogen receptors 18F-fuoroestradiol ƒ e.g. Breast cancer ƒ Dopamine receptors: 18F-fluoro-DOPA ƒ e.g. Prostate cancer, neuroendocrine tumors ƒ Benzodiazepine receptors: 18F-flumazenil ƒ e.g. Epilepsy ƒ Somatostatin receptors: 68Ga-DOTA TOC and NOC

More Promising PET Tracers ƒ Cellular oxygenation-hypoxia: 18F-MISO, 64CuATSM ƒ Hypoxia increases resistance to XRT ƒ Hypoxia leads to phenotypic heterogeneity

ƒ ƒ ƒ ƒ

Drug binding-sensitivity Gene expression/Gene therapy Cell death/apoptosis: Annexin Angiogenesis:18F-galacto-RGD ƒ targeting avB3 integrin expression, a critical angiogenic modulator

Clinical Applications for FDG PET and PET/CT ƒ PET with FDG = imaging modality allowing direct evaluation of the cellular glucose metabolism ƒ Neurology ƒ Brain Tumors ƒ HIV positive patients with neurological symptoms ƒ Epilepsy ƒ Neuropsychiatric disorders (dementias) ƒ Cerebrovascular disease ƒ Cardiology ƒ Myocardial perfusion: 13N-ammonia, 82Rb ƒ Myocardial viability: 18F-FDG

ƒ Oncology

Glycogen Glycogen Glucose Glucose

Hexokinase Hexokinase Glucose-6-P Glucose Glucose-6-P Glucose

Cell Cell membrane membrane and and capillary capillary

H Pentose-P H22O O ++ CO CO22 Pentose-P

Hexokinase Hexokinase FDG FDG

FDG FDG

FDG-6-P FDG-6-P

Normal Distribution of FDG ƒ ƒ ƒ ƒ ƒ ƒ

Brain: high uptake in the gray matter Myocardium: variable uptake Lungs: low uptake Mediastinum: low uptake Liver: low uptake GI tract: variable activity (esophagus, stomach, colon) ƒ Urinary tract: excretes FDG ƒ Muscular system: low uptake at rest

Cook GJR, et al: Semin Nucl Med 1996;26:308-314

Clinical Applications for PET in Oncology ƒ Most malignant tumors: ƒ Increased number of glucose transporter proteins ƒ Increased glycolytic enzyme levels Æ Increased FDG uptake compared to normal cells ƒ FDG PET became an established imaging modality for: ƒ Diagnosing malignancies ƒ Staging and restaging malignancies ƒ Monitor therapy ƒ Assess recurrence ƒ Surveillance ƒ Screening

Positron Decay

Instrumentation for PET Imaging

Dedicated PET tomographs Gamma Camera Based PET = Hybrid PET

Dedicated PET tomographs with BGO detectors (most commo

GE Advance

Anatomical & Molecular Imaging Are Complimentary

ƒ Limitations of CT: ƒ Size criteria for lymph nodes involvement ƒ Differentiation of unopacified bowel versus lesion ƒ Evaluation of tumors after therapy ƒ Equivocal lesions ƒ Limitations of FDG PET: ƒ Limited resolution ƒ Accurate localization of the abnormalities ƒ Physiological variations of FDG distribution ƒ Optimal interpretation: In conjunction with each other

Æ Integrated PET/CT is optimal and became available in year 2000

Integrated PET/CT Imaging Systems

CTI Reveal GE Discovery LS and ST Philips Gemini (GSO) CPS Biograph (BGO) (LYSO, time of flight) (BGO and LSO) ƒ Diagnostic CT Scanner ƒ Multislice (2 – 4 slices/rotation originally, now 8,16, …., 64) ƒ 0.5 seconds/rotation, helical Scan – 17 seconds/meter

Properties of common scintillation crystals Crystal

Effect

NaI (Tl)

BGO GSO

Density

Stopping power

3.67

7.13

6.7

7.40

51

75

59

65

Atomic #

LSO

Light output

Energy resol Spatial resol Scatter

100

15

25

75

Decay time

Dead time Count rate

230

300

30-60

3545

Yes

No

No

No

Hygroscopic

Integrated PET/CT Imaging System Benefit of the combined technique: 1) Attenuation correction with CT 2) Anatomical localization

Discovery LS orSTE (GE Healthcare) PET CT

Attenuation Correction Anatomical localization

Integrated PET-CT Scanners ƒ Spectrum of equipment available: ƒ The quality of the PET images depends on the PET system and protocol. ƒ Resolution of the integrated CT images depends on the CT system and the protocol. ƒ Issues: ƒ Optimal CT protocols (IV contrast, breathing pattern, etc..) ƒ Patient positioning ƒ Operation of PET-CT systems: RT versus CNMT ƒ Interpretation and reports: radiologist versus nuclear medicine physicians ƒ Cost and billing

Correction for Attenuation Artifacts ƒ Attenuation effects are more significant in coincidence imaging than SPECT because both annihilation photons must pass through the region without interaction. ƒ Methods: ƒ Calculated attenuation correction: e.g. Brain ƒ Measured attenuation correction using attenuation maps (transmission scan) obtained with various transmission sources: ƒ Typically sources of Ge-68 ƒ X-ray source Transmission Ge-68 rod sources on the GE Advance PET Scanner

Advantages of Correction for Attenuation ƒ Improvement of the anatomic delineation ƒ Lesions can be localized more accurately ƒ Necessary for semiquantitative evaluation with SUV ƒ May be helpful for specific clinical situation e.g. indeterminate pulmonary nodules e.g. monitoring therapy

no AC

AC

No AC

Correction for Attenuation Artifacts ƒ The quality of the images with attenuation depends of the accuracy of registration of the emission and transmission scan. ƒ Inaccurate repositioning of the patient between scans can be avoided by performing simultaneous or sequential transmission/emission scans without moving the patient from the imaging table. ƒ Motion of the patient is a problem. ƒ Optimal correction for attenuation can be obtained using integrated PET/CT systems.

An 81-year-old female presented with a left lung mass FDG PET without AC

FDG PET with AC Diagnosis: The apparent decreased uptake in the R MCA territory is due to patient’s motion between emission and transmission scan

Respiratory motion -Æ misregistration

With AC

Without AC

Patient shifted to the right for PET acquisition Æ misregistration (physiologic muscular uptake projects over the left femoral head

CT for Attenuation Maps ƒ High quality maps because of high photon flux ƒ Low current (10 mA) provides satisfactory attenuation maps. ƒ Short duration ƒ < 1 minute from base of the skull to mid-thigh with multidetector CT. ƒ Also provide anatomical maps for lesion localization ƒ Current of ~80 mA is a compromise for limited radiation dose ƒ Whole body dose equivalent ~ 700 mrem (7.0 mSv) ƒ Whole body dose equivalent for FDG (10 mCi) ~700 mrem ƒ Whole body dose equivalent for whole body PET-CT: ~ 4.8 years background radiation in US

Technical Protocol for whole body PET/CT (GE Discovery STE at VUMC)

ƒ Transmission CT ƒ 80 mA (fixed or adjust to patient’s weight) ƒ 130-140 kVp ƒ 40-90 msec ƒ 5 mm slices ƒ Pitch 3/1 ƒ No IV contrast ƒ Breath-hold at Tidal volume or normal breathing ƒ Emission PET ƒ 2D: 4 min/bed position ƒ 3D: 2min/bed ƒ Regional diagnostic CT with IV and oral contrast if indicated

Beyer T, et al. J Nucl Med 2004;45 (Suppl): 25S

Artifacts on CT-attenuated PET images ƒ Inaccurate co-registration due to: ƒ Random motion (but less likely with short transmission scan) ƒ Respiratory motion ƒ Curvilinear cold artifacts along diaphragm ƒ Inaccurate localization of lesion in the region of diaphragm (dome of liver versus lung bases) in 2% of patients Goerres GW et al. Radiology 2003;226:906-910. Osman MM et al. Eur J Nucl Med 2003;30:603-606. Osman MM et al. J Nucl Med 2003;44:240-243.

65 year-old with lung cancer s/p XRT to mediastinum 1 week earlier

Radiation esophagitis Curvilinear photopenia along diaphragm due to motion of diaphragm

Artifacts on CT-attenuated PET images ƒ Hot spots due to over-correction related to: ƒ ƒ ƒ

IV contrast Focal accumulation of oral contrast Metallic implants (dental, hardware…)

ƒ Overestimation of SUV values by up to 10% compared to Ge-68 based attenuation correction. Antoch G et al.J Nucl Med 2002;43:1339-1342. Cohade C et al. J Nucl Med 2003;44:412-416. Goerres GW et al. Eur J Nucl Med Molec Imag 2002;29:367-370. Nakamoto Y et al. J Nucl Med 2002;43:1137-1143. Antoch G et al. J Nucl Med 2004: 45 (Suppl): 56S.

SNM Procedure Guideline

SNM Guideline J Nucl Med 2006; 47 (May): 885

SNM Procedure Guidelines for FDG PET/CT ƒ ƒ ƒ

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Purpose Background Information and Definitions Procedure ƒ Patient Preparation ƒ Information Pertinent to Performing the Procedure (focused history) ƒ Radiopharmaceutical ƒ Image Acquisition Intervention Processing Interpretation Criteria Reporting Quality Control Sources of Error Qualification of Personnel

SNM Guideline J Nucl Med 2006;47:1227

Sources of False +/- Interpretations ƒ

ƒ

F+: Physiologic FDG uptake ƒ Lymphoid tissue ƒ Brown adipose tissue ƒ Glandular tissue ƒ Muscular system ƒ GI tract ƒ GU tract F+: Inflammation ƒ Therapy-related ƒ Therapy-related: Ostomies, drainage tubes, stents (percutaneous more common), radiation therapy , chemotherapy ƒ Trauma ƒ Infection ƒ Abscesses, Acute cholecystitis, Acute cholangitis, Acute pancreatitis (chronic pancreatitis but uncommon), Inflammatory bowel disease, Diverticulitis ƒ Granulomatous disease: TB, fungi

Sources of False +/- Interpretations ƒ False negative include: ƒ Small lesions (