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Positron Emission Tomography in Clinical
Oncology
Chun Ki Kim, M.D. Mount Sinai School of
Medicine New York, New York
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Commonly used PET Radiotracers

• F-18 FDG - Glucose metabolism
• C-11 Methionine - Amino acid transport
• - Incorporation of amino acid
• into protein fractions
• O-15 Water - Blood flow
• N-13 Ammonia - Blood flow
• Rb-82 - Blood flow

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Potential PET Radiotracers

• C-11 Thymidine Tumor cellular proliferation
  rate
• C-11 Aminoisobutyric acid Tumor amino acid
  uptake
• F-18 5-FU Prediction/evaluation of ChemoTx
• C-11 Tyrosine Tumor metabolism
• N-13 Glutamate Tumor metabolism
• C-11 Acetate Myocardial oxidative metabolism
• C-11 Palmitate Myocardial fatty acid
  metabolism
• F-18 FluoroDOPA Dopamine synthesis
• Many other receptor agents Dopamine, serotonin,
  opiate etc.

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PET Radiotracer approved by FDA

• F-18 FDG (fluoro deoxyglucose)
• ? Malignancy ? Glucose / FDG uptake

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NORMAL
TUMOR

• Overexpression of Glucose transporters
• Higher levels of Hexokinase
• Down-regulation of Glucose-6-phosphatase
• Anaerobic glycolysis, less ATP per glucose
  molecule,
• more glucose molecules needed for ATP
  production
• General increase in metabolism from high growth
  rates

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Malignancy ? Glucose/FDG uptake
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Gallium PET
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Metastatic Thyroid Ca. to Lung, Mediastinum, and
Skeleton
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General Indications for FDG-PET Tumor Imaging

• DDx Benign versus Malignant
• Staging Restaging
• Metastatic work up Rising tumor markers
• Monitoring treatment response
• Scar/necrosis/fibrosis vs. Recurrent/residual
  disease
• Grading/Prognosis
• Detection of unknown primary

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New Medicare Coverage Policy for FDG PET

• Lung Ca (NSC) Dx, Staging restaging
• Esophgeal Ca Dx, Staging restaging
• Colorectal Ca Dx, Staging restaging
• Lymphoma Dx, Staging restaging
• Melanoma Dx, Staging restaging,
• Non-covered for evaluating regional nodes
• Head Neck Ca Dx, Staging restaging

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Lung Cancer

• Dx Solitary Pulmonary Nodule
• Staging
• Metastatic work-up

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Solitary Pulmonary Nodule

• Incidence detected by CXR 130,000/year.
• 50-60 Benign
• 20-40 Invasive nodule biopsy
• Resection.

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CT an indeterminant LUL nodule.
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Efficacy of PET Solitary Pulmonary Nodule

• Sensitivity 97
• Specificity 78
• (Meta-analysis of gt40 articles Gould et al.
  JAMA 2001)

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False Positives Active Infection/Inflammati
on TB Pneumonia Cryptococcosis Histoplasmosis
Aspergillosis Inflammatory
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Staging
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60/M Lung Ca.
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62y/o Lung Ca. with adrenal mass
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Colorectal CancerClinical Indications for PET
Imaging

• Staging before primary resection?
• Detection of Lesions after Primary Resection
• Staging before resection of recurrent disease.
• Rising CEA in the absence of a known source.
• Equivocal/residual lesion on conventional
  imaging.
• Patient is clinically symptomatic, but CEA is
  normal.
• Monitoring treatment response (pre-op post-op)

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Staging before resection of recurrent disease
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63 y/o woman with a H/O Colon Ca. and liver
metastases
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79/M. Resection of Rectal Ca (Dukes B) 4 mos
earlier, ? CEA, CT possible local relapse.
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T1
T2

• F/68
• H/O Colon Ca.
• Rising CEA
• CT/MRI multiple cysts

T1 enhanced
T1 enhanced
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Sagittal Transverse Coronal
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• YW Colon Ca
• 3/00 (-) CT
• 5/00 rising CEA
• 6/00 () PET
• 7/00 CT

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58/M - S/P Colon Ca Rising CEA
Coronal Coronal Transverse
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58/M - S/P Colon Ca Rising CEA
Hemangioma
Local recurrence
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• 48y/o with Colon Ca.
• S/P Primary resection.
• S/P Resection of liver
  
• lesion
• Now with ? CEA
• CT (-) for mets

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• 48y/o with Colon Ca.
• S/P Primary resection.
• S/P Resection of liver
  
• lesion
• Now with ? CEA
• CT (-) for mets

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N. G. 8/15/00 Colon cancer with a Hx of UC Proven
mesenteric carcinomatosis
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1756441
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Huebner et al. J Nucl Med 2000411177-1189
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Huebner et al. J Nucl Med 2000411177-1189
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Colorectal Cancer A possible algorithm
CT evidence of resectable disease in patient
suitable for surgery
Whole Body PET imaging
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Colorectal Cancer A possible algorithm
Further evaluation of CT abnormality
All sites negative
CT evidence of resectable disease in patient
suitable for surgery
Whole Body PET imaging
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Colorectal Cancer A possible algorithm
Further evaluation of CT abnormality
All sites negative
CT evidence of resectable disease in patient
suitable for surgery
Whole Body PET imaging
PET CT and other sites negative
Surgery
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Colorectal Cancer A possible algorithm
Further evaluation of CT abnormality
All sites negative
CT evidence of resectable disease in patient
suitable for surgery
Whole Body PET imaging
PET CT and other sites negative
Surgery
ve at multiple Sites
Non-surgical management
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Staging
44/F with Colon Ca, S/P primary resection.CT
multiple liver mets and a lung nodule
Treated with systemic chemoTx instead of
intra-arterial chemoTx.
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Colorectal CancerClinical Indications for PET
Imaging

• Detection of Lesions
• Staging before resection of recurrent disease.
• Rising CEA in the absence of a known source.
• Equivocal/residual lesion on conventional
  imaging.
• Patient is clinically symptomatic, but CEA is
  normal.
• Monitoring treatment response (pre-op post-op)
• Staging before primary resection?

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S/P ChemoRx
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Before 2mo after Adjuvant
chemo and radioTx Prior to surgery for rectal Ca.
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Optimal time to scan after treatment??
Residual FDG activity after treatment Not always
active tumor

• Uptake may be seen in inflammatory tissue /
  macrophages.

• 1 month after Chemo.
• PET findings at 1 mo CT findings at 3 mos
• Findlay et al. J Clin Oncol 1996
• Several months after RT?

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Lymphoma Indications for PET Imaging

• Dx
• Staging
• Monitoring treatment response
• Recurrence?

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Evaluation of early therapeutic response Is
treatment effective?FDG uptake represents cell
viability.

• FDG uptake can be markedly decreased or even
  completely suppressed after 1 or 2 cycles of
  chemotherapy
• Early determination is important To avoid the
  toxicity of ineffective therapy. To allow
  selection of a new therapeutic regimen.

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1846641 Lymphoma Before
After 2 cylcles of Chemo
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Lymphoma Before After 2
cylcles of Chemo
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56y/o Lymphoma
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Before
1 month after XRT
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Esophageal/Gastro-esophageal CancerClinical
Indications for PET Imaging

• Pre-op staging
• Monitoring treatment response
• Suspected recurrence
• Prognostication

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Esophageal/ Gastro-esophageal CancerClinical
Indications for PET Imaging

• Pre-op staging
• CT Limited sensitivity
• EUS More accurate for assessing local
  invasion and regional nodal mets.
• Limitations stenosis,
• celiac,
• right hepatic lobe, peritoneum

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Evaluation of N stage of patients with Esophageal
Cancer 48 patients underwent esohagectomy and
lymph node dissection (2 field35pts, 3
field13pts)
(Choi et al J Nucl Med 2000)
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Evaluation of metastases in Esophageal Cancer
CT versus PET
CT PET Kole 1998 Lymph
nodes 62 90 Resectability 65 88 Choi
2000 Lymph nodes 78 86 N
staging 60 83 Luketich 1999 Distant
mets 63 84
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Rt. Paratracheal Subcarinal Lt.
Gastric Common hepatic Celiac
Rt. Paratracheal Subcarinal Lt.
Gastric Common hepatic Celiac
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62F Gastric Ca. S/P Resection CT Recurrence PET
performed to exclude other sites of tumor
Ultrasound confirmed a liver mets Surgery
cancelled and the patient treated with Chemo
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Gastro-esophageal CancerClinical Indications
for PET Imaging

• Pre-op staging
• Monitoring treatment response
• Suspected recurrence
• Prognostication

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49M large squamous esophageal Ca. Echo-endoscopy
an enlarged node
Before sagittal
coronal After Radiochemo
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Gastro-esophageal CancerClinical Indications
for PET Imaging

• Pre-op staging
• Monitoring treatment response
• Suspected recurrence
• Prognostication

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45M S/P esophagectomy, Patient is clinically
asymptomatic ? alkaline phosphatase
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Gastro-esophageal CancerClinical Indications
for PET Imaging

• Pre-op staging
• Monitoring treatment response
• Suspected recurrence
• Prognostication

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Surviavl based on initial PET scan identification
of distant versus local disease only (Luketich
et al Ann Thorac Surg 199968)
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Pancreatic CancerPotential Indications for PET
Imaging

• DDx Chronic pancreatic mass vs. Cancer
• Staging Nodal mets and liver mets.
• Monitoring treatment response
• Prognostication

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53/F Pancreatic mass
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51F CT (1) Mass forming pancreatitis vs
Cancer (2) Hepatic Hemangioma vs
Metastasis
Coronal Sagittal
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Pancreatic CancerDDx Chronic pancreatic mass
vs. Cancer Delbeke et al J Nucl Med 1999
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Brain Tumor

• Grading
• Prognosis/Survival.
• Necrosis or Residual disease after radiation
  therapy?

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High GradeLow Grade
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Kim CK et al. J Neuro-Oncol 1991
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Thyroid Cancer Thyroglobulin () Iodine-131 scan
(-)

• FDG PET scan is useful.

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FDG-PET
I-131
M
L
M
V
I
Anterior Posterior
2 Coronal slices
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62 y/o male S/P Resection of transglottic right
laryngeal cancer R/O Recurrence
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FDG PET Imaging Determination of the site of
unknown primary tumor2030
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Prediction of tumor response to treatmentWill
the tumor respond to treatment?

• Labeled Estrogen
• F-18 5-Fluorouracil (5-FU)

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FDG-PET Tumor Imaging

• DDx Is the lesion benign or malignant?
• StagingRe-staging
• Evaluation of early therapeutic response
• Scar/Necrosis vs recurrent/residual disease after
  surgery.Scar/Necrosis vs recurrent/residual
  disease after XRT.
• Histologic grading / Prognosis.
• Detection of unknown primary.

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Summary PET

• Safe.
• Shows all the organ systems of the body with one
  image.
• Decreases the number of diagnostic (imaging)
  procedures.
• Diagnoses disease often before it shows up on
  other tests.
• Shows the progress of disease and how the body
  responds to treatment.
• Reduces or eliminates ineffective or unnecessary
  surgical or medical treatments and
  hospitalization.
• Significantly reduces multiple medical costs and
  avoids needless pain to the patient.

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The influence of blood glucose levels on 18FDG
uptake in cancer(Crippa et al. Tumori
199783748-752)

• 8 patients - 20 liver metastases on CT
• PET 1 Fasting (92.410.2)
• All 20 were () on PET.
• PET 2 Glucose infusion (15813.8)
• 6/20 undetected, and 10 lesions localized less
  clearly.

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• 70-years-old female smoker
• CT showed Rt mid lung mass and inhomogeneity
  throughout the liver

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Coronal Sagittal
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55 y/o womanDxed with colon ca.S/P resection
2 yrs agoCEA level is risingNo evidence of
recurrence. CT normal.