Nuclear Oncologygyfor medical students

Jiraporn Sriprapaporn,M.D.Di N l di iDiv Nuclear medicine

Siriraj Hospital Mahidol University Bangkok

N l O lNuclear Oncology

Conventional Tumor ImagingImaging

WB+ PlanarSPECTSPECTSPECT/CT

Onco PET (Positron Emission Tomography)

PETPET/CT

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Objectives of Tumor Imaging

DiagnosisgStagingGuiding for biopsyFollow up & monitoringFollow-up & monitoring treatmentDetect tumor recurrence

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Nuclear Oncology

Functional Med LN

SensitiveWhole body evaluationWhole-body evaluationSpecific-some tumors

ADR

RP LNp

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Conventional Tumor Imaging

Ga 67 citrate I 131 (DTC)Ga-67 citrateTl-201T 99 MIBI

I-131 (DTC)I-131 MIBG (neural crest tumors)Tc-99m MIBI

Tc-99m Tetrofosmin

crest tumors)Receptor imaging eg somatostatineg. somatostatin Radiolabelled MoAb imaging

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imaging

G lli 67Fever of unknown origin

(FUO)Gallium-67 (FUO)

Nonspecific for infection-inflammation & tumorsMechanism : bind to iron transport proteins egMechanism : bind to iron transport proteins eg. transferrin, lactoferrinE ti kid & l b lExcretion: kidneys & large bowelDose :5-10 mCi IV.Scan at 24-72 hr. pi.Tumors : Lymphoma (Hodgkin's lymphoma)Tumors : Lymphoma (Hodgkin s lymphoma),Bronchogenic carcinoma, Malignant melanoma, Hepatoma

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Hepatoma

Objectives of Ga-67 Imaging in lymphoma

StagingStagingFollow-up & monitoringFollow up & monitoring treatmentDetect tumor recurrence

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G lli 67 & L hGallium-67 & Lymphoma

Right paratracheal lymphadenopathyRight paratracheal lymphadenopathy

Planar Images SPECT ImagesJ Sriprapaporn

Planar Images SPECT Images

T 99 MIBI & Tl 201Tc-99m MIBI & Tl-201

Nonspecific tumor imagingp g gCan be applied in several types of ttumorsRapid information-imaging at 10-Rapid information imaging at 1020 min. pi.Uptake in viable tumor but not in scarred tissue

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scarred tissue

Objectives of Tumor Imaging

Localize site for biopsyDetermine grade of malignancy Evaluate the response of preoperativeEvaluate the response of preoperative CMT or RTDetermine residual tumor &/or local recurrencerecurrenceDifferentiate post-therapy tissue necrosis o fib o i f om lo l e en e

J Sriprapaporn or fibrosis from local recurrence

I di iIndications

Brain tumorsBronchogenic carcinomaThyroid carcinomaThyroid carcinomaParathyroid adenomaB & ft tiBone & soft tissue sarcomaBreast cancerLymphoma : Head & neck cancers

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Head & neck cancers

Bone Tumor PO. with Recurrence

Tc-99m MDP Tl-201

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P h id AdParathyroid Adenoma

T 99 T 99 MIBITc-99m Tc-99m MIBI

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I 131 MIBG SI-131 MIBG Scan

I-131 MetaiodobenzylguanidineN d li lNoradrenaline analogLocalizes in adrenergic tissues, catecholamine-producing tumors & theirmetastasesFirst synthesized by Wieland et al. in 1979Patient Preparation:Patient Preparation:

Withdrawal of drugs interfering MIBG uptakeLugol’s solution to block thyroid uptake of free

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Lugol s solution to block thyroid uptake of free iodide

I 131 MIBG A id TI-131 MIBG-Avid Tumors

Pheochromocytoma/ eoc o ocyto a/ParagangliomaNeuroblastomaM d ll th id iMedullary thyroid carcinoma (MTC)(MTC)Carcinoid tumor

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Bone Scan in Neuroblastoma20-2-44 (PreRx) 4-6-44 (PostRx)

3 yo girl

20 2 44 (PreRx) 4 6 44 (PostRx)

3 yo girlNBM stage IV with multiple bone metastases 2-44

Pre & post CMT 4 courses (induction)(induction)

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I-131 MIBG in NeuroblastomaI-131 MIBG in Neuroblastoma

3 i l NBM t IV ith lti l b t 2 44

ANT POST

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3 yo girl, NBM stage IV with multiple bone metas 2-44Pretreatment staging

I-131 MIBG in NeuroblastomaI-131 MIBG in Neuroblastoma

Girl, 3 yo.Neuroblastoma stage IV with multiple bone metastases 2-44Post 4 courses of CMT (induction)

ANT POST ANT POST

( )F/U after Rx

J Sriprapaporn 28-2-44 (PreRx) 6-6-44 (PostRx)

J Sriprapaporn J Sriprapaporn 2011

Wh i PET?What is PET?

PET =Positron Emission TomographyTomographyPET emitters emit positron from theirpositron from their nucleiPositron then reacts withPositron then reacts with electron annihilation

2 gamma photons2 gamma photons, 511 keV moving in opposite direction

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opposite direction

Principal Positron Emitters

PET Radionuclides Physical T1/2PET Radionuclides Physical T1/2

C-11N-13

20 min10 minN-13

O-1510 min2 min

F-18 110 min

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Steps for PET PET IMAGING

Imaging

Production of positron-emitting Rdnemitting Rdn.Labeling a selected compound with a

CYCLOTRONcompound with a positron-emitting Rdn.Administration into a

RADIOPHARM

Administration into a patient (IV, inhalation) Imaging the patient PET SCANNER

PATIENT

ag g t e pat e tReconstruction & display (Quantitation) COMPUTER

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p y (Q )

PET CT I iCT PETPET/CT ImagingPET-CT ImagingCT PETImaging

Scout CTScout CCT low mA*PET scan-Non ACPET scan Non ACPET-ACPET(AC)-CT

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PET(AC) CT

I d PET/CT SIntegrated PET/CT Scan

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PET/CTPET/CT Scanners

Siriraj

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FDG F 18 FDGFDG F-18 FDG

First synthesis by Ido et al (1974) at Brookhaven National Laboratory brain scan at HUP in 1976FDG= Fluorodeoxyglucose, glucose analogue, represents glucose metabolismrepresents glucose metabolism

FDG enters the cells using the same pathway as glucose (glucose transporter p y g (g pproteins) [R23: Mochizuki T, et al. JNM 2001]but is not used in glycolysis and ismetabolically trapped inside the cells aftermetabolically trapped inside the cells after phophorylation (FDG-6-phosphate). FDG is excreted in large quantities by kidney

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FDG is excreted in large quantities by kidney unlike glucose.

FDG MetabolismFDG Metabolism

1Glycolysis

Glut

2

1G-6-P isomerase (Buck AK JNM 2004)

GlycolysisGlut

Enz1 = Hexokinase -- Phosphorylation

2

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Enz1 = Hexokinase -- Phosphorylation

Enz2= Glucose-6-phosphatase

Tumor cells higher glycolytic rate than normal tissue.

Normal FDG PET/CT ImagingNormal FDG PET/CT Imaging

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PET/CT SPECTPET/CT vs SPECT

Higher sensitivityHigher image qualityBetter anatomical localization with CTBetter anatomical localization with CT Whole-body imaging y g gMore accurate quantificationM t b li i i t ll l l lMetabolic imaging at cellular level

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Mechanism of F-18 FDG UptakeMechanism of F 18 FDG Uptake

Malignant cells have increased gglucose utilization due to

O i f b lOver expression of membrane glucose transporter receptors, especially Glut-1 and Glut-3 on surface of tumor cells.Increased hexokinase activityIncreased hexokinase activityDecreased level of G-6-phosphatase

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Clin Indications for PET/CT

DDx single pulmonary nodule, Grading tumorsStagingStagingMonitoring treatmentgDDx post therapeutic fibrosis & residual/recurrent tumorresidual/recurrent tumor

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Table1: Medicare-approved l i di i fOncologic Indications for PET

*Special Medicare restrictions exist for these indications

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p

Griffeth LK 2005

PET-CT Reimbursement in Thailand [26-11-07]

From 1 JAN 2008, 40,000 Baht/test for only 2Indications: Colon cancer & NSCLCIndications: Colon cancer & NSCLC

Colon cancer1. KPS > 70S 02. Suspected tumor recurrence due to rising CEA3. Negative or unclear CT or MRI of abdomen to

document recurrencedocument recurrence4. Abnormal CT or MRI supposed to be completely

resected. (for curative aim)If th fi t PET CT i di t d i ti th5. If the first PET-CT scan as indicated is negative, the PET study can be repeated at duration not less than 3 mos.

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PET-CT Reimbursement in Thailand [26-11-07]

Non-small cell lung cancer 1. KPS > 702. Staging for curative aim

2.1 Clinical stage T2-3,N1-2 and Mo2.2 The patient had previous CT scan p pof chest adrenal and bone scan done.(no distant metas)

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I i T h iImaging Techniques

Fasting for 4-6 hrs prior to PET/CT studyInject F-18 FDG 10-20 mCi IVInject F-18 FDG 10-20 mCi IVWait for 45-60 minutes to scanScanning time is about 30 minutes to complete PET/CT studies. SUVcomplete PET/CT studies. SUVmax

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FDG PET-Single Pulmonary Nodule (SPN)

To identify pulmonary malignancy:y p y g ysens 82-100%, spec 67-100%, and accuracy 79-94%

Figure: SPN NSCLCFigure: SPN NSCLC

CT scan: a small nodule in the LULLULPET-FDG: intense accumulation

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PET for N-Staging of NSCLC

CT: Left NSCLC w a pathologic AP window node (N2) (white), and a non-pathologic retrocaval-pretracheal contralateral mediastinal node (N3) (yellow). ( ) (y )PET-FDG images: increased tracer accumulation within both nodes, consistent with metastases. Thus PET is more sensitive than CT in detect small

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Thus, PET is more sensitive than CT in detect small hypermetabolic LN metas.

FDG PETi i CMonitoring CMT Response

Baseline PET study is required!

Intense tumor uptake and nodal uptake of FDGp

Reduced metabolicReduced metabolic activity response to treatmenttreatment

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Colorectal CA w Liver M P P RMetas.: Pre-Post Rx

Patient with colorectal metastases and previous left hemihepatectomyhemihepatectomy. 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 radiofrequencyC CT after radiofrequency ablation shows a large area without contrast enhancement(arrow). D PET/CT f i fD PET/CT fusion after radiofrequency ablationindicates complete ablation of the recurrent metastasis with a

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photopenic lesion.

Colorectal CA w Liver Metas-Recurrence

A CT 3 month after radiofrequency ablation h f l lshows no sign of local recurrence.

B PET/CT 3 month after radiofrequency ablation d t t l l t t

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demonstrates a local recurrent tumor.

Malignant Melanoma w Disseminated Metastases

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