Positron Emission Tomography
in Clinical Oncology
Chun Ki Kim, M.D.Chun Ki Kim, M.D.
Mount Sinai School of MedicineMount Sinai School of Medicine
New York, New YorkNew York, New York
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
• [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.
Potential PET Radiotracers
PET Radiotracer approved by FDA
• [F-18] FDG (fluoro deoxyglucose)
Malignancy ~ Glucose / FDG uptake
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
Malignancy
Glucose/FDG uptake
Gallium PET
Metastatic Thyroid Ca. to Lung, Mediastinum, and Skeleton
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
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
Lung Cancer
Dx: Solitary Pulmonary NoduleStagingMetastatic work-up
Solitary Pulmonary Nodule
• Incidence detected by CXR: 130,000/year.
50-60%: Benign
20-40%: Invasive nodule biopsy
Resection.
CT: an indeterminant LUL nodule.
Efficacy of PET Solitary Pulmonary Nodule
• Sensitivity = 97%• Specificity = 78%
(Meta-analysis of >40 articles: Gould et al. JAMA 2001)
False Positives:
Active Infection/Inflammation
TB
PneumoniaCryptococcosisHistoplasmosis
AspergillosisInflammatory
Staging
60/M: Lung Ca.
62y/o Lung Ca. with adrenal mass
Colorectal Cancer:Clinical 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)
Staging before resection of recurrent disease
63 y/o woman with a H/O Colon Ca. and liver metastases
79/M. Resection of Rectal Ca (Dukes B) 4 mos earlier,
CEA, CT: possible local relapse.
T1 T2
T1 enhanced T1 enhanced
• F/68• H/O Colon Ca.• Rising CEA• CT/MRI;
multiple cysts
Sagittal Transverse Coronal
YW: Colon Ca• 3/00: (-) CT • 5/00: rising CEA
• 6/00: (+) PET
• 7/00: CT
58/M - S/P Colon CaRising CEA
Coronal Coronal Transverse
58/M - S/P Colon CaRising CEA
Local recurrence
Hemangioma
• 48y/o with Colon Ca.• S/P Primary resection.• S/P Resection of liver lesion
• Now with CEA • CT: (-) for mets
• 48y/o with Colon Ca.• S/P Primary resection.• S/P Resection of liver lesion
• Now with CEA • CT: (-) for mets
N. G. 8/15/00Colon cancer with a Hx of UCProven mesenteric carcinomatosis
1756441
Huebner et al. J Nucl Med 2000;41:1177-1189
Huebner et al. J Nucl Med 2000;41:1177-1189
Colorectal Cancer: A possible algorithm
CT evidence of resectable disease in patient suitable for surgery
WholeBodyPET imaging
Colorectal Cancer: A possible algorithm
CT evidence of resectable disease in patient suitable for surgery
WholeBodyPET imaging
Further evaluation of CT abnormality
All sites negative
Colorectal Cancer: A possible algorithm
CT evidence of resectable disease in patient suitable for surgery
WholeBodyPET imaging
Further evaluation of CT abnormality
Surgery
All sites negative
PET = CT and other sites negative
Colorectal Cancer: A possible algorithm
CT evidence of resectable disease in patient suitable for surgery
WholeBodyPET imaging
Further evaluation of CT abnormality
Non-surgical management
Surgery
All sites negative
+ ve at multipleSites
PET = CT and other sites negative
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.
Staging:
Colorectal Cancer:Clinical 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?
S/P ChemoRx
Before 2mo after Adjuvant chemo and radioTxPrior to surgery for rectal Ca.
Optimal time to scan after treatment??
Uptake may be seen in inflammatory tissue / macrophages.
Residual FDG activity after treatment:Not always active tumor
• 1 month after Chemo.
PET findings at 1 mo ~ CT findings at 3 mosFindlay et al. J Clin Oncol 1996
• Several months after RT?
Lymphoma: Indications for PET Imaging
Dx Staging Monitoring treatment response Recurrence?
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.
1846641Lymphoma
Before
After2 cylcles ofChemo
Lymphoma
Before
After2 cylcles ofChemo
56y/o : Lymphoma
Before 1 month after XRT
Esophageal/Gastro-esophageal Cancer:
Clinical Indications for PET Imaging
Pre-op stagingMonitoring treatment responseSuspected recurrence Prognostication
Esophageal/ Gastro-esophageal Cancer:Clinical Indications for PET Imaging
Pre-op stagingCT: Limited sensitivityEUS: More accurate for assessing local
invasion and regional nodal mets.
Limitations: stenosis,
celiac,
right hepatic lobe, peritoneum
(Choi et al: J Nucl Med 2000)
Evaluation of N stage of patients with Esophageal Cancer: 48 patients underwent esohagectomy and lymph node dissection (2 field=35pts, 3 field=13pts)
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%
Rt. Paratracheal
Subcarinal
Lt. Gastric
Common hepatic& Celiac
Rt. Paratracheal
Subcarinal
Lt. Gastric
Common hepatic& Celiac
62F: Gastric Ca. S/P ResectionCT: RecurrencePET performed to exclude other sites of tumor
Ultrasound: confirmed a liver metsSurgery cancelled and the patient treated with Chemo
Gastro-esophageal Cancer:Clinical Indications for PET
Imaging
Pre-op stagingMonitoring treatment responseSuspected recurrence Prognostication
Before
sagittal coronal
AfterRadiochemo
49M: large squamous esophageal Ca.Echo-endoscopy – an enlarged node
Gastro-esophageal Cancer:Clinical Indications for PET
Imaging
Pre-op stagingMonitoring treatment responseSuspected recurrencePrognostication
45M: S/P esophagectomy, Patient is clinically asymptomatic alkaline phosphatase
Gastro-esophageal Cancer:Clinical Indications for PET
Imaging
Pre-op stagingMonitoring treatment responseSuspected recurrencePrognostication
Surviavl based on initial PET scan identification of distant versus local disease only: (Luketich et al: Ann Thorac Surg 1999;68)
Pancreatic Cancer:Potential Indications for PET Imaging
DDx: Chronic pancreatic mass vs. Cancer Staging: Nodal mets and liver mets. Monitoring treatment response Prognostication
53/F: Pancreatic mass
51F: CT: (1) Mass forming pancreatitis vs Cancer (2) Hepatic Hemangioma vs Metastasis
Coronal Sagittal
Pancreatic Cancer:DDx: Chronic pancreatic mass vs. Cancer
Delbeke et al: J Nucl Med 1999
Brain Tumor
Grading Prognosis/Survival.Necrosis or Residual disease after
radiation therapy?
High Grade
Low Grade
Kim CK et al. J Neuro-Oncol 1991
Thyroid Cancer Thyroglobulin (+)
Iodine-131 scan (-)
FDG PET scan is useful.
IV
ML
FDG-PET I-131
Anterior Posterior
M
2 Coronal slices
62 y/o male S/P Resection of transglottic right laryngeal cancerR/O Recurrence
FDG PET Imaging
Determination of the site of unknown primary tumor
20~30%
Prediction of tumor response to treatment:
Will the tumor respond to treatment?
Labeled Estrogen [F-18] 5-Fluorouracil (5-FU)
FDG-PET Tumor Imaging
DDx: Is the lesion benign or malignant? Staging:
Re-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.
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.
The influence of blood glucose levels
on 18FDG uptake in cancer(Crippa et al. Tumori 1997:83:748-752)
8 patients - 20 liver metastases on CT• PET 1: Fasting (92.4±10.2)
All 20 were (+) on PET.
• PET 2: Glucose infusion (158±13.8)6/20 undetected, and 10 lesions localized less clearly.
• 70-years-old female smoker • CT showed Rt mid lung mass and inhomogeneity
throughout the liver
Coronal Sagittal
55 y/o womanDx’ed with colon ca.S/P resection 2 yrs agoCEA level is risingNo evidence of recurrence. CT: normal.