This document discusses advances in oncological PET imaging. It begins by outlining limitations of current PET/CT imaging related to false positives, false negatives, and radiation exposure. It then describes several advances in PET imaging including new radiotracers for tumor characterization, instrumentation improvements, software enhancements to reduce radiation dose, and hybrid PET/MRI imaging. The document provides examples of how various new radiotracers beyond FDG can provide clinical benefits for tumor imaging and characterization.
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Advances in oncological PET/CT Imaging
1. Dr. Hussein Farghaly, MDDr. Hussein Farghaly, MD
Assistant professor and ConsultantAssistant professor and Consultant
nuclear Medicinenuclear Medicine
Advances in oncological PETAdvances in oncological PET
ImagingImaging
2. Outline
Introduction
Limitations of PET/CT imaging
Advances of PET/CT Imaging:
New PET radiotracer
PET/CT protocols
Soft Wear Enhance the specificity
Insturmentation
PET/MRI
PEM
3. IntroductionIntroduction
FDG PET/CT has emerged as a powerful imaging tool for the detection of various cancers.FDG PET/CT has emerged as a powerful imaging tool for the detection of various cancers.
The combined acquisition of PET and CT has synergistic advantages over PET or CT aloneThe combined acquisition of PET and CT has synergistic advantages over PET or CT alone
and minimizes their individual limitations.and minimizes their individual limitations.
It is a valuable tool for staging and restaging of some tumors and has an important role in theIt is a valuable tool for staging and restaging of some tumors and has an important role in the
detection of recurrence in asymptomatic patients with rising tumor marker levels and patientsdetection of recurrence in asymptomatic patients with rising tumor marker levels and patients
with negative or equivocal findings on conventional imaging techniques. It also allows forwith negative or equivocal findings on conventional imaging techniques. It also allows for
monitoring response to therapy and permitting timely modification of therapeutic regimens. Inmonitoring response to therapy and permitting timely modification of therapeutic regimens. In
about one third of the patients, the course of management is changedabout one third of the patients, the course of management is changed
4. Clinical Impact of PET/CT
Advantages of PET/CT over Conventional anatomical imaging:
• Characterizing lesions difficult to biopsy
• Detecting occult cancer
• Determining extent of cancer and response to therapy
Significant clinical impact
More accurate diagnosis
Avoidance of unnecessary tests, and (potentially) harmful procedures
Better treatment or management (PET - CT changes management in about one third of cancer
patient)
Is FDG PET/CT a completely perfect test?
5. Limitations in FDG – PET/CTLimitations in FDG – PET/CT
imagingimaging
Due to FDG:Due to FDG:
False positiveFalse positive
False negativeFalse negative
Radiation exposure from radiotracer (8Radiation exposure from radiotracer (8
mSv)mSv)
Due to instrumentation:Due to instrumentation:
mis-registration (motion artifact)mis-registration (motion artifact)
low spatial resolutionlow spatial resolution
Radiation exposure from CT (7 -25 mSv)Radiation exposure from CT (7 -25 mSv)
Long study timeLong study time
6. Limitations in FDG – PET/CTLimitations in FDG – PET/CT
imagingimaging
False positive:False positive:
““Normal” uptakeNormal” uptake (head & neck, muscle, brown fat, GI/GU uptake)(head & neck, muscle, brown fat, GI/GU uptake)
false-positive FDG uptake can occur in PET/CT in relation tofalse-positive FDG uptake can occur in PET/CT in relation to
granulomatous disease or inflammation. Some benign tumors, such asgranulomatous disease or inflammation. Some benign tumors, such as
colonic adenomas and fibroids, may also demonstrate intense FDG uptakecolonic adenomas and fibroids, may also demonstrate intense FDG uptake
False negative:False negative:
Small lesions (partial volume loss)Small lesions (partial volume loss)
Hypometabolic lesions (low grade tumor, well differentiated NET,Hypometabolic lesions (low grade tumor, well differentiated NET,
mucinous secreting tumor, RCC, some low grade lymphoma likemucinous secreting tumor, RCC, some low grade lymphoma like
small lymphocytic lymphoma, peripheral T-cell lymphomasmall lymphocytic lymphoma, peripheral T-cell lymphoma
Elevated serum glucoseElevated serum glucose
9. Glucose metabolism [Glucose metabolism [1818
F]FDGF]FDG
Protein synthesis C-11-methionine
Membrane function [Membrane function [1111
C]CholineC]Choline
ProliferationProliferation [[1818
F]FLTF]FLT
HypoxiaHypoxia [[1818
F]FMISOF]FMISO
[18F]FAZA[18F]FAZA
[64Cu]ATSM[64Cu]ATSM
ApoptosisApoptosis [[1818
F]Annexin VF]Annexin V
AngiogenesisAngiogenesis [[1818
F]NGR-peptideF]NGR-peptide
Neuroendocrine tumorsNeuroendocrine tumors [[110110
In]OctreotateIn]Octreotate
[68Ga] DOTATOC[68Ga] DOTATOC
TRACERS for TUMOR CHARACTERIZATIONTRACERS for TUMOR CHARACTERIZATION
Advances in PET RadiotracerAdvances in PET Radiotracer
10. Normal distribution
of FDG and C-11
Methionine
C-11-methionineC-11-methionine
Benjamin et al; 2010 Anticancer Ther. 10(5), 609–613 (2010)
Posterior fossa glioma.
11. C-11-methionineC-11-methionine
(A) 18F-FDG; (B) contrast-enhanced MRI; (C) 11C-MET PET. Glioblastoma in the right
frontal lobe, which is hard to delineate in the 18F-FDG PET. However, amino-acid PET
with 11C-MET clearly shows the lesion with excellent tumor to background contrast.
Benjamin et al; 2010 Anticancer Ther. 10(5), 609–613 (2010)
A B
C
12. left frontal grade II fibrillary astrocytoma (post-left frontal grade II fibrillary astrocytoma (post-
surgery and post-radiotherapy)surgery and post-radiotherapy)
C-11-methionineC-11-methionine
Benjamin et al; 2010 Anticancer Ther. 10(5), 609–613 (2010)
14. 11C-choline11C-choline
Fifty-five-year-old patient with increasing PSA level (1.43 μg/l), 27 months after radical
prostatectomy (Gleason score8). Coronal (left), axial (middle), and sagittal (right) fused image
projections of PET/CT scans. Focal 11C-choline uptake (a) in right (bold arrow) and left (thin
arrow) iliac region revealed lymph node involvement, not observed with 18F-FDG PET (b).
Richter et al;, Mol Imaging Biol (2009)
22. Outline
PET/CT principle
Indeterminate lung nodules
Lung cancer
Staging and Restaging of known tumor
Monitoring therapy
Early detection of tumour recurrence
Impact on radiation therapy planning
23. Indeterminate lung nodules
Accounts for ≈ 20% of newly diagnosed lung cancer
CXR and CT: not accurate to differentiate benign from
malignant non-calcified pulmonary nodules that are
between 1-3 cm in diameter
Initial presentation in 20% - 30% of lung cancer
Morphologic stability over 2 years: reliable sign of
benignity:
Doubling time of malignant nodules: 30-400 days
Doubling in volume results in 26% increase in
diameter
24. Visual Analysis:Visual Analysis: nodule activity vs mediastinal blood pool activinodule activity vs mediastinal blood pool activi
Quantitative analysis: SUV (standardized uptake value)Quantitative analysis: SUV (standardized uptake value)
[[1818
F]FDG PETF]FDG PET
Measure of metabolic activity of SPNMeasure of metabolic activity of SPN
SUV = 7.3
CT [18
F]FDG PET
A SPN with SUV more than 2.5 is considered to be malignant
25. PIOPILN Study
Prospective investigation of PET in lung nodules
90 patients from 5 centers with indeterminate nodules (CT)
Size range: 0.7 to 4 cm
All nodules had histology: 67% were malignant
PIOPLIN and other studies: SUV > 2.5 = visual (FDG uptake > mediastinal
blood pool)
Sensitivity: 90-100% Specificity: 69-95%
False positive: Active granuloma
False negative: Bronchioalveolar, mucinous carcinoma, carcinoid
Hyperglycemia (decreases uptake by up to 50%)
Lowe VJ et al. J Clin Oncol 1998;16:1075-1084.
Nomori H et al. Lung cancer 2004;45:19-27.
Herder GJ et al. Eur J Nucl Med Mol Imag 2004;31:1231-1236.
Lowe VJ et al. J Nucl Med 1994;35:1771-1776.
Nomori H et al. Ann Thorac Surg 2005;79:984-988.
26. Diagnostic Accuracy of FDG PET and CT for the
Characterization of Lung Nodule
344 patients for which definite diagnosis was obtained
Prevalence of malignancy: 53%
Average size: 16 mm
PETPET CTCT
Sensitivity 91.7% 95.6%
Specificity 82.3% 40.6%
Fletcher JW et al. J Nucl Med 2008;49 (2):179-
185
32. Question
What should be done next?
A. Biopsy
B. Reassure the patient that the nodule is benign
C. Follow-up with CT at 3-6 months interval for
2 years
D. Follow-up with chest X-ray in 6 months
33. Question
What should be done next?
A. Biopsy
B. Reassure the patient that the nodule is benign
C. Follow-up with CT at 3-6 months interval
for 2 years
D. Follow-up with chest X-ray in 6 months
34. ACCP Evidenced-Based Clinical Practice
Guidelines: Recommendation for FDG PET
PET recommended: Probability of cancer low to
moderate (5%-60%) and an indeterminate
nodule measures at least 8-10 mm.
PET NOT recommended: SPN that has a high
probability of malignancy (>60%) or nodule <
8-10 mm
35. Staging NSCLC
T staging: tumor size
T1 < 3 cm
T2 > 3 cm
T3 > 3 cm with chest wall, pleural, or pericardial extension
T4 with invasion of adjacent organs
N staging: nodal metastases
N0: no nodes
N1: ipsilateral hilar nodes
N2: ipsilateral mediastinal or subcarinal nodes
N3: contralateral nodes or scalene/supraclavicular nodes
M Staging: distant metastases
M0: no distant metastases
M1: distant metastases present
36. FDG PET for Staging
T staging:
The extent of the primary tumor determines therapeutic management.
Imaging is done to assess the size of the tumor and the extent of pleural,
chest wall or mediastinal invasion.
CT and MRI are useful for confirming gross chest wall and mediastinal
invasion. But they are inaccurate in differentiation between anatomic
contiguity and subtle invasion.
FDG PET alone: limited for T staging due to poor anatomic resolution,
lack of anatomical landmark.
PET/CT: improve staging by clearly demarcating the actual extent of the
tumor and involvement of chest wall, diaphragm, mediastinal pleura or
pericardium or main bronchus (T3 staging).
Padma; et al, 2011.
37. T staging cont.:
similarly, it is useful to determine the involvement of mediastinal,
vertebral and vital structures, such as the great vessels, trachea,
esophagus or heart (T4 staging).
Also it is used to evaluate additional pulmonary nodules in the same
lobe/ipsilateral lung having primary lung cancer, and determine the
likelihood of malignancy in these nodules.
CT is rarely able to differentiate between reactive and malignant
pleural effusion whereas malignant pleural effusion showed FDG
uptake in PET (stage M1a).
It also has a role in guiding biopsy in patient with disease recurrence.
38. 66 year-old with right hilar mass
Primary lung ca
with atelectasis
40. N staging:
•The precise characterization of
mediastinal lymph nodes is crucial
for determining nodal (N) stage
and thus resectability in patients
with NSCLC.
•CT and MRI: limited by size
criteria.
• FDG PET: best to detect tumor
in normal size lymph nodes
41. CTCT
Depending on size criteria on CT a lymph node with a short-axis
diameter greater than 1 cm is considered enlarged and a
predictor for metastasis. However, this method has proven
inaccurate. In one study, 44% of metastatic lymph nodes in
patients with NSCLC measured less than 1 cm, and 77% of
patients without metastatic lymph nodes had a lymph node
measuring greater than 1 cm in the short-axis diameter.
Several meta-analyses have reported low sensitivities and
specificities of CT in the assessment of mediastinal lymph-node
involvement, ranging from 50% to 65% and from 65% to 85%,
respectively.
Prenzel et al; 2003.
42. FDG PET/CTFDG PET/CT
Depending on the metabolic activity within the lymph node
FDG PET can characterize mediastinal LN.
PET positive mediastinal findings should be histologically
or cytologically confirmed due the fact that FDG is also
taken by inflammatory process.
In patients with negative mediastinal PET images invasive
staging can be omitted and it is estimated that the introduction
of PET has reduced the number of mediastinoscopies by 65%
Also in case of central tumors, PET hilar N1 disease, low FDG
uptake of the primary tumour, invasive staging with
mediastinoscopy remains indicated.
44. Staging PET/CT in 74-year-old woman with 2.6-cm left lower lobe SCCStaging PET/CT in 74-year-old woman with 2.6-cm left lower lobe SCC
Diagnostic axial contrast-enhanced CT scan
shows multiple small subcentimeter lymph
nodes scattered throughout mediastinum,
primarily in lower left paratracheal region.
Fused axial PET/CT image shows uptake in
lower left paratracheal lymph nodes and 3-
mm lower right paratracheal lymph node
With metastatic involvement, confirmed at mediastinoscopy. Given presence of
contralateral lymph node metastases, patient received chemotherapy and radiation
instead of surgical
45. Initial staging PET/CT for 56-year-old man with 1.8-cm
adenocarcinoma in right upper lobe and long history of sarcoidosis
Axial contrast-enhanced CT scan
shows 1.8-cm right upper lobe
nodule with extensive
mediastinal and hilar
lymphadenopathy
Fused axial PET/CT image confirms intense
uptake in right upper lobe nodule and lymph
nodes. Lymph node biopsies performed during
mediastinoscopy showed only granulomatous
inflammation from sarcoidosis and no evidence
of tumor
Given this finding, patient was sent for curative resection
46. M Staging:
Common metastases to adrenals, skeleton, liver, brain.
FDG PET is superior to conventional imaging:
Detect metastases > ~7 mm when CT and MRI are normal or
equivocal
Detect unsuspected distant metastases: ~13% of patients
Stage I: 7.5%
Stage II: 18%
Stage III: 24%
Change management: 18% of cases
Peterman RM et al N Engl J Med 2000;343:254-261
Baum RP et al. Q J Nucl Med 2004;48:119-142.
47. PET/CT for the Characterization of Adrenal
Masses in Patients with lung Cancer
Giles et al; AJR:192, April 2009
48.
49. Bury T et al. Eur J Nucl Med 1998;25:1244-1247.
56. maxSUV: 2.6
48 year-old female with a pulmonary mass
48 year-old female with a pulmonary mass
57.
58. Histological TypeHistological Type
CarcinoidCarcinoid
Pure Bronchioloalveolar Car (BAC),Pure Bronchioloalveolar Car (BAC),
mucinous camucinous ca
neuroendocrine tumorneuroendocrine tumor
Well differentiated typeWell differentiated type
Lesion Dimension:Lesion Dimension: Small lesion < 6-8 mmSmall lesion < 6-8 mm
% of viable neoplastic% of viable neoplastic
cells in SPNcells in SPN
Limitations of FDG-PET for Lung NoduleLimitations of FDG-PET for Lung Nodule
Characterization and NSCLC:Characterization and NSCLC:
False-negative resultsFalse-negative results
HyperglycemiaHyperglycemia:: > 200 mg/dl = PET not performed> 200 mg/dl = PET not performed
61. 52 years woman with an infiltrative lung nodule
maxSUV: 1.9
62. Question
What is the differential diagnosis?
A. Neuroendocrine tumor
B. Bronchioalveolar carcinoma
C. Infection
D. All of the above
63. Question
What is in the differential diagnosis?
A. Neuroendocrine tumor
Bronchioalveolar carcinoma
C. Infection
D. All of the above
64. New Techniques to overcome LimitationsNew Techniques to overcome Limitations
of FDG-PET in NSCLCof FDG-PET in NSCLC
Imprecise physiologic and anatomic registration, most common
adjacent to the diaphragm and heart, can lead to misregistration
artifact. (RESPIRATORY GATING)
Many processes with increased metabolic activity, such as
infection and inflammation, show increased uptake on PET.
(DUAL TIME POINT TECHNIQUE)
Tumor with low FDG uptake (Carcinoid,Carcinoid, BAC, mucinous ca,
neuroendocrine tumor, Well differentiated type) OTHER PET
RADIOTRACER.
66. Dual-Time-Point F-18 FDG PET/CT
E SUV 5.7
D SUV 7.1
PET/CT imaging was performed
60 and 120 minutes after injection
67. Seth Kligerman1 and Subba Digumarthy: Staging of Non–Small Cell Lung Cancer Using
Integrated PET/CT. AJR 2009; 193:1203–1211.
Dominique Delbeke: Role of FDG PET and PET/CT Imaging in Indeterminate
Pulmonary Nodules and Lung CancerCongreso Chileno de Medicina Nuclear, Santiago,
Chile 13-14 Noviembre 2008.
Padma S, Shanmuuga P. and Shamily G.: Role of PET in carcinoma lung evaluation:.
Journal of cancer rearach and therapeutics-April-June 2011-Volume 7-Issue 2.
Didier Lardinois: Pre- and intra-operative mediastinal staging in non-small-cell lung
cancer. Swiss Med Wkly. 2011;141:w13168.
Kiyoshi Shibuya, Kenzo Hiroshima and Takehiko Fujisawa: Comparison of
Endobronchial Ultrasound, Positron Emission Tomography, and CT for Lymph Node
Staging of Lung Cancer. Chest 2006;130;710-718
Khaled Alkhawaldeh,, Hans-J Biersack,, Anna Henke,, and Samer Ezziddin: Impact of Dual-Time-
Point F-18 FDG PET/CT in the Assessment of Pleural Effusion in Patients With Non–
Small-Cell Lung Cancer. Clin Nucl Med 2011;36: 423–428)
ReferencesReferences
Posterior fossa glioma. Contrast-enhanced axial (A)
and sagittal (C) MRI images show a conglomerate ring-enhancing
lesion (arrow) that was mistaken for a tuberculoma. Axial fused FDG
PET/CT image (B) shows low-grade FDG uptake (arrow). Axial fused
11C methionine PET/CT image (D) shows uptake (arrow), consistent
with a high-grade malignancy. Note normal uptake in the pituitary gland
Contrast-enhanced CT scan(A,B) show a left frontal
grade II fibrillary astrocytoma (post-surgery and post-radiotherapy)
with a peripherally enhancing cavity (arrow) that is equivocal for
tumor residue/post-radiotherapy changes, which was also the case
on a contrast-enhanced MRI (not shown). Axial FDG PET/CT image
(C) shows no radiotracer uptake (arrow). Axial 11C methionine PET/
CT (D) shows increased uptake anteriorly (arrow), and this was later
proven to be tumor residue on biopsy
CT scan, FDG-PET scan, and 11C-choline-PET scan images of lung cancer and pulmonary
tuberculosis (the deep-black color in the PET scan images represents an SUV of 4). The diagnosis
was confirmed by pathologic and bacteriologic examinations. Primary lung cancer was visualized by
both FDG and 11C-choline (one arrow each). The metastatic lymph nodes in the mediastinum were
clearly visualized by 11C-choline (two arrows) but were faintly visualized by FDG (one arrow). In
contrast, tuberculosis was clearly visualized by FDG (six arrows) but was faintly visualized by
11C-choline. The high SUV of FDG in the myocardium (in the image of lung cancer) was caused by
hyperglycemia. Choline 11C-choline.
A) 18F-misonidazole (FMISO) PET scans obtained
3 d apart in patient with head and neck cancer show large
variations in size and distribution of hypoxic regions between
scans. Tumor volume was defined by viable tumor tissue that
showed 18F-FDG uptake. (B) Intensity-modulated radiotherapy
dose distributions in color-wash display of patient whose
sequential 18F-misonidazole PET scans were similar. Hypoxic
target volume was defined from first scan (outlined in red), and
boost dose of 14 Gy was delivered to this zone in addition to
70-Gy prescription dose.
(With functional imaging development, it becomes possible to increase radiation dose to radioresistant areas (located inside tumor volume) using radiotherapy dose-painting. This strategy is particularly suitable for prostate cancer where tumor hypoxia plays a major role in the resistance of these tumors to radiation.
In order to develop intratumoral hypoxia targeting by radiotherapy dose-painting areas, we should characterize changes in hypoxia before treatment and during radiotherapy.
If hypoxia does not change during radiotherapy, radiotherapy dose-painting strategy by an &quot;integrated&quot; boost is performed.
If hypoxia varied (increasing or incomplete regression), a &quot;final&quot; boost strategy of radiotherapy dose-painting(IMRT, stereotactic brachytherapy or high dose rate) after a first fractionated IMRT could be considered.
)
37%
Grade 1 geographic miss
If any part of the GTVPET is outside the GTVCT
26%
Grade 2 geographic miss
if &lt;90% of the PTVPET receives &gt;95% prescribed dose based on planning with CT data
The American College of Chest Physicians (ACCP
Both primary staging and restaging mediastinal lymph-node after induction treatment
A, B, Fused axial PET/CT image shows uptake in
lower left paratracheal lymph nodes and 3-mm
lower right paratracheal lymph node with
metastatic involvement, which was confirmed at
mediastinoscopy. Given presence of contralateral
lymph node metastases, patient received
chemotherapy and radiation instead of surgical
resection.