Basic Nuclear Oncologic Imaging_MD4-NS_2017

Nuclear Medicine Studies for MD4_NS

Jiraporn Sriprapaporn, M.D.

Division of Nuclear Medicine

Department of Radiology

Siriraj Hospital 16 February 2017

Nuclear Oncology

Lung Scan & RNV

By Jiraporn Sriprapaporn

Clinical Indications for Tumor Imaging

Localization of tumor eg. parathyroid scan

Confirm nature of tumor eg. I-131 MIBG scan for pheochromocytoma

Staging & monitoring known malignancies eg. Ga-67 for lymphoma

Guiding for biopsy site

DDx post therapeutic fibrosis & residual/recurrent tumor

Detecting tumor recurrence, especially in the presence of elevated

tumor markers

PET: DDx benign vs malignant, staging, monitoring, restaging, guiding

RT planning, tumors of unknown primary

Procedure Guideline_Snmmi.org By Jiraporn Sriprapaporn

Radiopharmaceuticals for Non-PET Oncologic Applications

REF : modified from The Requisites


Most commonly used PET radiopharmaceutical

oncology = F-18 fluorodeoxyglucose (F-18 FDG )

FDG is glucose analogue.

F-18 is cyclotron-produced radionuclide.

Relatively short physical half-life as compared to

SPECT agents.

PET/CT Imaging

PET: Positron emission tomography By Jiraporn Sriprapaporn

Parathyroid adenoma***

Thyroid carcinoma*

Breast cancer**

Bone & soft tissue sarcoma

Bronchogenic carcinoma

Brain tumors

Head & neck cancers

Thyroid Cancer


B S G I

Fig. 1A Comparison of dense and nondense breast imaging with MMG and BSGI

Images from mammography (A) and breast-specific gamma imaging (BSGI) (B) in 48-

year-old woman with heterogeneously dense breast tissue show infiltrating ductal

carcinoma (IDC) in superior left breast.

Images from mammography (C) and breast-specific gamma imaging (BSGI) (D) in 53-

year-old woman with predominantly fatty breast tissue show IDC in 2-o'clock position of

left breast.

Rechtman LR, et al. AJR 2014

Dense breasts Fatty breasts


Non-PET Oncologic Imaging_Jiraporn

Role of Parathyroid Scintigraphy

• 99mTc-sestamibi assessment has a well defined clinical role in PHPT > SHPT & THPT

• PHPT: Parathyroid adenoma

– Preop localization: for focused surgery and for

minimally invasive radioguided parathyroidectomy.

– Persistent or recurrent disease post surgery, NM is a first line examination before reoperation.

• 99mTc-sestamibi assessment in secondary HPT is not clearly established.

Ectopic parathyroid adenoma Nuclear scan has great benefit !



Guidelines for Parathyroid Scintigraphy

2012



• Single isotope, dual-phase technique

– Tc-99m MIBI or Tc-99m tetrofosmin, early & delayed

• Double isotopes, subtraction technique

– Tl-201 & Tc-99m pertechnetate

– Tc-99m MIBI & Tc-99m pertechnetate

• Combined techniques

A. Tc-99m pertechnetate thyroid only

B. Tl-201 or Tc-99m MIBI thyroid + parathyroid

Parathyroid = B-A

Parathyroid Scintigraphy: Technique

*Same position



Mechanism of Tc-99m MIBI Uptake

• Parathyroid adenomas typically have a very high metabolic rate for their size and show high avidity for labeled MIBI.

• The presence of mitochondria-rich oxyphil cells and increased vascularity presumably accounts for 99mTc-MIBI trapping

• However, a small number of oxyphil cells in some adenomas may account for rapid washout of 99mTc-MIBI from the adenoma.

Lorberboym M, JNM 2003 By Jiraporn Sriprapaporn


Subtraction Technique Dual-phase Technique


Giuliano Mariani et al. J Nucl Med 2003;44:1443-1458

Parathyroid Scintigraphy (Dual-tracer, Subtraction Technique : 99mTcO4 & 99mTc MIBI)



Primary Hyperparathyroidism (Dual-phase Tc-99m MIBI Imaging)

(a) Delayed washout in the right inferior parathyroid adenoma

(b) Early washout in a large inferior thyroid adenoma

Eslamy HK, RADGr 2008

Early Delayed



Dual-isotope, subtraction techn.

• Persistent hyperparathyroidism

following right lobectomy due to

ectopic parathyroid adenoma

Early & delayed Tc-99m MIBI scan

• Parathyroid adenoma shows increased

Tc-99m MIBI uptake with delayed

washout at right lower pole

Single isotope, dual-phase technique

99mTcO4- 99mTc MIBI

After subtraction



• A 35-year-old man with ESRD S/P

cadaveric KT (21/12/2007) & total

parathyroidectomy with autoimplanted

right lower gland to right forearm on

17/11/2013 due to SHPT.

• PATHO: Parathyroid hyperplasia at right

upper, right lower and left upper

parathyroid glands but labelled left lower

parathyroid gland was reactive LN.

• After surgery he still has persistent high

level of PTH level (before surgery 1,289

pg/ml and after surgery 2,071 pg/ml.

• Parathyrtoid scan (25/11/2013): Parathyroid Adenoma at left inferior pole

• PATHO:

Tc-99m MIBI Parathyroid scan & SPECT/CT images.


Clinical Indications for F-18 FDG PET/CT

A. Differentiating benign from malignant lesions

B. Searching for an unknown primary tumor

C. Staging known malignancies

D. Monitoring the effect of therapy on known malignancies

E. DDx post therapeutic fibrosis & residual/recurrent tumor

F. Detecting tumor recurrence, especially in the presence of elevated

tumor markers

G. Guiding for biopsy site

H. Guiding radiation therapy planning

Procedure Guideline_Snmmi.org By Jiraporn Sriprapaporn

Diagnosis - Solitary pulmonary nodule (SPN) benign vs

malignant

Staging - NSCLC, lymphoma (HL & NHL) advantages over conventional imaging upstaging or down staging

Evaluate treatment response - Lymphoma DDx viable vs

fibrosis

Detection of recurrence - Colorectal cancer (in setting of rising serum CEA rising, normal or equivocal imaging)

Treatment planning

Indications for reimbursement in Thailand: NSCLC staging & CRC recurrence

PET/CT Scan for Oncologic Applications


What is PET?

PET =Positron Emission Tomography

PET emitters emit positron from their nuclei

Positron then reacts with electron annihilation 2 gamma photons, 511 keV moving in opposite direction


Principal Positron Emitters

PET Radionuclides Physical T1/2

(minutes)

C-11 20

N-13 10

O-15 2

F-18 110


Steps for PET Imaging

Production of positron-emitting Rdn.

Labeling a selected compound with a positron-emitting Rdn.

Administration into a patient (IV, inhalation)

Imaging the patient

Reconstruction & display (Quantitation)

CYCLOTRON

COMPUTER

PET/CT SCANNER

RADIOPHARM

PATIENT


Integrated PET/CT Scan


PET/CT Scanners

Siriraj


F-18 FDG

First synthesis by Ido et al (1974) at Brookhaven National Laboratory brain scan at HUP in 1976

FDG= Fluorodeoxyglucose, glucose analogue, represents glucose metabolism

FDG enters the cells using the same pathway as glucose (glucose transporter proteins) [R23: Mochizuki T, et al. JNM 2001] but is not used in glycolysis and is metabolically trapped inside the cells after phophorylation (FDG-6-phosphate).

FDG is excreted in large quantities by kidney unlike glucose.


FDG Metabolism

Enz1 = Hexokinase -- Phosphorylation

Enz2= Glucose-6-phosphatase

Tumor cells higher glycolytic rate than normal tissue.

1

1

2

2

Glycolysis

Glycolysis

Glut

Glut

G-6-P isomerase (Buck

AK JNM 2004)


Mechanism of F-18 FDG Uptake

Malignant cells have increased glucose utilization due to

↑ Vascular flow : More radiotracer available for uptake

↑ Glucose transporter (GLUT) - especially Glut-1 and Glut-3

on surface of tumor cells.

: More FDG moves into tumor cells

↑ Hexokinase II : More FDG-6-P production, leading to

metabolic trapping

↓ G-6-Pase : Less intracellular de-phosphorylate FDG-6-P

F-18 FDG F-18 FDG-6 Phosphate


PET/CT Imaging

Advantages

• PET - functional imaging high sensitivity for early disease detection, predict prognosis

• High target/background ratio

• PET/CT = one-stop investigation, WB evaluation Cost effective (appropriate use)

Disadvantages

High cost limited use

Limited reimbursement

Not widely available

Radiation exposure

Relatively low specificity (false positive – ex. TB, inflammation) – needs clinical correlation


Appropriate PET Scan Timing

Post biopsy 1 Wk

Post surgery 4-6 Wks

Post CMT 4-6 Wks

Post ERT 4-6 Months

• Alavi A. PET and PET/CT: A Clinical Guide

• Cook GJ, et al. Sem Nucl Med 2004

To avoid false-positive uptake due to inflammatory process !!

Radiotracer: F-18 FDG (fluorodeoxyglucose), glucose analogue

Route of administration: IV

Patient preparation:

Avoid strenuous exercise for several days

Low carbohydrate intake a day before

Fasting 4-6 hrs, good hydration

Control serum glucose

Blood sugar: should not > 150 mg/dl, > 200 mg/dl reschedule

Scan Time: 60 min following radiotracer injection

PET/CT Scan: Patient Preparation & Technique


PET-CT Imaging CT PET

Scout CT

CT low mA*

PET scan-Non AC

PET-AC

PET(AC)-CT

Topogram

Sequences of PET/CT imaging

http://www.med.harvard.edu/JPNM/chetan/petct/petct.html

Or SUR : Standardized Uptake Ratio

Semi-quantitative measurement of degree of F-18 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 increase glucose uptake high SUV


SUV (Standardized Uptake Value)

Concentration in ROI (uCi/g) SUVbw = --------------------------------------- Injected Dose (mCi) / BW (kg).

PET/CT: Radiation Exposure

The radiation dose of FDG is approximately 2 × 10−2 mSv/MBq according to ICRP publication 106 [28], i.e. about 3–4 mSv for an administered activity of 185 MBq. (5 mCi) [EANM Guideline]

Authors F-18 FDG PET Dose

(mSv) CT Dose (mSv)

Total PET/CT RAD

Dose

Kaushik A, 2013 [24125986]

-Female

-Male

14.4

11.8

Khamwan K, 2010 4.40 14.45 18.85

Huang B, 2009 [19251940]

-Female

-Male

6.40

6.60

19.10

19.70

25.5

26.3

Quan V, 2007 7 18 25

Brix G, 2005 [15809483] 25

Whole-body PET/CT Low-dose CT --> To minimize radiation to the Pts.

Normal FDG PET/CT Imaging


Physiologic F-18 FDG Uptake

Brain

Salivary glands and lymphoid tissues in the head and neck

Thymus, especially in children

Thyroid (faint)

Lactating breast, Areola

Myocardium

Liver-spleen

Skeletal and smooth muscles

Gastrointestinal tract (e.g., esophagus, stomach, or bowel)

Kidneys & urinary tract structures

Female genital tract (e.g., uterus during menses or corpus luteal cyst)


PET/CT Pitfalls False-positive findings

• Physiologic uptake that may lead to false-

positive interpretations

• Brown fat

• Infection (TB, sarcoidosis)

• Inflammation

• Benign neoplasms

• Hyperplasia or dysplasia

• Artifacts

False-negative findings: Small size (<2 times the resolution of the

system)

Recent chemotherapy or radiotherapy

Recent high-dose steroid therapy

Hyperglycemia and hyperinsulinemia

Some low-grade tumors (e.g., sarcoma, lymphoma, or brain tumor)

Tumors with large mucinous components

Hepatocellular carcinomas (HCC), especially well differentiated tumors

Some genitourinary carcinomas, especially well differentiated

Prostate carcinoma, especially well-differentiated tumors

Some neuroendocrine tumors, especially well-differentiated

Differentiated thyroid carcinomas

Bronchioloalveolar carcinomas (BAL)

Lobular carcinomas of the breast

Skeletal metastases, especially osteoblastic or sclerotic

Some osteosarcomas


Single pulmonary nodule (A)

Lung cancer- NSCLC – Staging (A) ***

Colorectal cancer – tumor recurrence (A) ***

Lymphoma – staging & Rx response (A)

Head & neck cancer – tumor recurrence (A)

Esophageal cancer – staging (A)

Melanoma – staging & tumor recurrence (A)

Thyroid cancer – tumor recurrence (B)

Clinical Indications of F-18 FDG PET/CT

A = well established, lots of literature support By Jiraporn Sriprapaporn

From 1 JAN 2008, 40,000 Baht/test for only 2

Indications: Colon cancer & NSCLC

Colorectal cancer 1. KPS > 70

2. Suspected tumor recurrence due to rising CEA

3. Negative or unclear CT or MRI of abdomen to document recurrence

4. Abnormal CT or MRI supposed to be completely resected. (for curative aim)

5. If the first PET-CT scan as indicated is negative, the PET study can be repeated at duration not less than 3 mos.

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


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

Non-small cell lung cancer

1. KPS > 70

2. Staging for curative aim

2.1 Clinical stage T2-3,N1-2 and Mo

2.2 The patient had previous CT scan of chest

adrenal and bone scan done. (no distant metas)


FDG PET for Single Pulmonary Nodule (SPN)

To identify pulmonary malignancy:

sens 82-100%, spec 67-100%, and accuracy 79-94%

Figure: SPN NSCLC CT scan: a small nodule in the LUL

PET-FDG: intense accumulation

Auntminnie.com By Jiraporn Sriprapaporn

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).

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.

Auntminnie.com By Jiraporn Sriprapaporn

Lymphoma: FDG PET for Monitoring CMT Response

Intense tumor uptake

and nodal uptake of FDG

Reduced metabolic

activity response to treatment

Baseline PET study is required!

Colorectal CA w Liver Metastasis:

Pre-Post Rx

Patient with colorectal metastases s/p left hemihepatectomy.

A. CT scan shows two hypodense nodules with contrast enhancement.

B. PET/CT fusion indicates a metastatic recurrent tumor beside a scar after operation.

C. CT scan after radiofrequency ablation (RFA) shows a large area without contrast enhancement (arrow).

D. PET/CT fusion after RFA indicates complete ablation of the recurrent metastasis with a photopenic lesion.

CT images PET/CT fusion images

Colorectal CA w Liver Metastasis

Recurrence

A. CT scan 3 months RFA shows no sign of local

recurrence.

B. PET/CT scan 3 months after RFA demonstrates a

local recurrent tumor.

DTC PO & RAI Rx with High Tg but negative I-131 TBS

I-131 Total-body scan

I-131 is good for well diff. tumors.

F-18 FDG is good for poorly diff. tumors.


Malignant Melanoma with

Disseminated Metastases


Ga-67 citrate – Lymphoma

Tc-99m MIBI – Parathyroid adenoma

I-131 – Differentiated thyroid cancer (DTC)

I-131 MIBG – Neural crest tumors

F-18 FDG – Several cancers

Nuclear Oncology

Important Tumor-imaging agents

SPECT

PET


Clinical Indications for Tumor Imaging

Localization of tumor eg. parathyroid scan

Confirm nature of tumor eg. I-131 MIBG scan for pheochromocytoma

Staging & monitoring known malignancies eg. Ga-67 for lymphoma

Guiding for biopsy site

DDx post therapeutic fibrosis & residual/recurrent tumor

Detecting tumor recurrence, especially in the presence of elevated

tumor markers

PET: DDx benign vs malignant, staging, monitoring, restaging, guiding

RT planning, tumors of unknown primary


NSCLC: Staging *

Colorectal cancer: Suspected tumor recurrence *

Lymphoma: Staging, monitoring, post complete

treatment

Others: Breast cancer, esophageal cancer, thyroid

cancer, malignant melanoma, bone & soft tissue sarcoma etc.


Common Malignant Tumors for PET/CT Evaluation

* Can be reimbursed in Thailand

PET/CT Pitfalls False-positive findings

• Physiologic uptake that may lead to false-

positive interpretations

• Brown fat

• Infection (TB, sarcoidosis)

• Inflammation

• Benign neoplasms

• Hyperplasia or dysplasia

• Artifacts

False-negative findings: Small size (<2 times the resolution of the

system)

Recent chemotherapy or radiotherapy

Recent high-dose steroid therapy

Hyperglycemia and hyperinsulinemia

Some low-grade tumors (e.g., sarcoma, lymphoma, or brain tumor)

Tumors with large mucinous components

Hepatocellular carcinomas (HCC), especially well differentiated tumors

Some genitourinary carcinomas, especially well differentiated

Prostate carcinoma, especially well-differentiated tumors

Some neuroendocrine tumors, especially well-differentiated

Differentiated thyroid carcinomas

Bronchioloalveolar carcinomas (BAL)

Lobular carcinomas of the breast

Skeletal metastases, especially osteoblastic or sclerotic

Some osteosarcomas


Basic Nuclear Oncologic Imaging_MD4-NS_2017

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