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  1. 1. PET SCAN IN ONCOLOGY DR. ARNAB BOSE Dept. of Radiotherapy NRS Medical College, Kolkata 1
  2. 2.  Imaging often is the best means of noninvasivelyidentifying and assessing tumors. With informationgleaned from imaging studies, the prognosis can beestablished and treatment decisions made with greatercertainty. Broadly stated, cancer imaging can be performedusing anatomic or functional imaging methods. 2
  3. 3.  The traditional imaging of the patient with cancer,and the most established methods, are based onanatomic imaging. However, interest is increasing in more functionalmethods in cancer imaging. Further, several anatomic imaging methods offerfunctional components that complement the anatomic method. Hybrid images, derived from and displaying bothfunctional and anatomic data, also are becoming more widelyavailable, often coming from the same hybrid imaging machine. 3
  4. 4.  Anatomic imaging normally detects a phenotypic alterationthat is sometimes, but not invariably, associated with cancer—a mass. However, with anatomic imaging, we often do notknow whether masses are the result of malignant or benignetiologies, as in solitary pulmonary nodules or borderline-sizelymph nodes. Similarly, small cancers are undetectable with traditionalanatomic methods, because they have not yet formed a mass. 4
  5. 5.  After surgery, it is even more difficult to assess for thepresence of recurrent tumor with anatomic methods. Post-treatment scans are complicated by the need forcomparisons with normal anatomy to detect alteredmorphologic findings as a result of cancer. Anatomic methods do not predict the response to treatmentand do not quickly document tumors responding to therapy. 5
  6. 6.  Positron Emission Tomography ( P E T ), a functionalimaging method, helps to address many of the limitations ofanatomic imaging, andwhen combined with anatomic images in fusion images,is emerging as a particularly valuable tool, providing bothanatomic precision and functional information in a single imageset. 6
  7. 7.  PET provides information on the metabolic function oforgans or tissues by detecting how cells process certaincompounds such as glucose. Most cancer cells metabolizeglucose at a much higher rate than normal tissues. Bydetecting increased radio-labelled glucose metabolism with ahigh degree of sensitivity, PET identifies cancerous cells, evenat an early stage, when other imaging modalities may missthem. 7
  8. 8.  In a typical PET study, one administers a positron emittingradionuclide by intravenous injection. The radionuclidecirculates through the bloodstream to reach a particular organ. The positrons emitted by the radionuclide travels a distanceof a few millimeters in tissue before it collides with anegatively charged electron. This collision annihilates theentire mass of the positron and electron, generating twophotons with energy of 511 KeV each. 8
  9. 9.  These two photons travel at the speed of light in exactlyopposite directions (i.e.180 degrees apart). Coincident detection of these two photons by two oppositelypositioned detectors in the PET scanner results in images witha much higher resolution compared with the conventional,single-photon nuclear medicine studies and produces thepossibility of quantitative measurement of the tracer uptake in avolume of interest. 9
  10. 10. detector array  PET machines are composed of a ring of detectors within which the patient isgamma photon positioned . positron  The gamma photons emitted travel at the speed of light. Rather thanradiotracer register the gamma photons as two separate events, the PET machine registers them as a paired event.  It does this through the establishment of time windows. If two gamma photons are detected within the same (small) time window, the camera records them as coming from the same annihilation event. As the gamma photons travel at 180 o to each other, the camera draws a line of flight between the two events and determines that the annihilation must have occurred along this line. 10
  11. 11.  The PET machine generates transverse images depictingthe distribution of positron emitting radionuclides in the patientand uses annihilation coincidence detection to obtainprojections of the activity distribution. The transverse imagesare obtained through the process of filtered back-projection. Detectors used for coincidence detection in modern PETmachines are scintillators made of bismuth germanate (BGO)or lutetium oxyorthosilicate doped with cerium (LSO:Ce)that transform the 0.511 MeV gamma ray energy into visiblephotons detected by photomultiplier tubes (PMTs). 11
  12. 12.  The radionuclides used in PET studies are produced bybombardment of an appropriate stable nuclide with protonsfrom a cyclotron, thereby producing positron emittingradionuclides that are subsequently attached to clinicallyuseful biological markers. 12
  13. 13.  The 18F radionuclide attached to the2-fluoro-2-deoxy-D-glucose (FDG) molecule is the biologicalmarker most commonly used in studies involving glucosemetabolism in cancer diagnosis and treatment(2-[18F] fluoro-2-deoxy-d-glucose). Tumor imaging with FDG is based on the principle ofincreased glucose metabolism of cancer cells. 13
  14. 14.  Like glucose, FDG is taken up by the cancer cells throughfacilitative glucose transporters (GLUTs). Once in the cell, glucose or FDG is phosphorylatedby hexokinase to glucose-6-phospate or FDG-6-phosphate,respectively. Expression of GLUTs and hexokinase, as well as the affinityof hexokinase for phosphorylation of glucose or FDG, isgenerally higher in cancer cells than in normal cells. 14
  15. 15.  Glucose-6-phosphate travels farther down the glycolytic oroxidative pathways to be metabolized, in contrast to FDG-6-phosphate, which cannot be metabolized. In normal cells,glucose-6-phosphate or FDG-6-phosphatecan be dephosphorylated and exit the cells. In cancer cells,however, expression of glucose-6-phosphatase is usuallysignificantly decreased, and glucose-6-phosphate or FDG-6-phosphate therefore can become only minimallydephosphorylated and remains in large part within the cell. Because FDG-6-phosphate cannot be metabolized, it istrapped in the cancer cell as a polar metabolite, and itconstitutes the basis for tumor visualization on PET. 15
  16. 16. NORMAL TUMOROver expression of Glucose transportersHigher levels of HexokinaseDown-regulation of Glucose-6-phosphataseAnaerobic glycolysis, less ATP per glucose molecule, more glucose molecules needed for ATP productionGeneral increase in metabolism from high growth rates 16
  17. 17.  A potential range of clinical scenarios in oncology for which18F-FDG-PET has shown to be worthwhile includes:i) The non-invasive characterization of the likelihood ofmalignancy of mass lesions, which are not readily amenable tobiopsy, or for which biopsy attempts have already failed.ii) The detection of cancer in patients at significantly increasedrisk of malignancy on basis of elevated tumor markers, clinicalsymptoms or signs but in whom routine tests have failed todetect a cancer. 17
  18. 18. iii) Staging of high-risk malignancy amenable to potentiallycurative therapy for which disease extent is critical to treatmentselection.iv) Planning of highly targeted therapy where delineation ofdisease is critical to efficient and safe treatment delivery andthereby, therapeutic success.v) Assessment of therapeutic response in diseases with asignificant likelihood of treatment failure, and for which earlierdemonstration of therapeutic failure may benefit the Surveillance of high-risk malignancies or evaluation atclinical relapse where salvage therapies exist and for whichearly intervention may be curative or prolong life. 18
  19. 19.  It is important to recognize that, being a tracer of glucosemetabolism, 18F-FDG is not a ‘specific’ radiotracer for imagingmalignant disease. There are several benign conditions and many physiologicalprocesses that lead to increased uptake of this tracer. These include, but are not limited to,normal wound healing,infection and inflammation,active muscle contraction during the uptake period, andactivated brown fat. 19
  20. 20.  Normal organs, including the brain, liver, kidneys and bonemarrow have relatively high 18F-FDG uptake, even underfasting conditions, and this provides background activity thatmay mask small lesions or malignancies with low glucosemetabolism. Such malignancies include some neuroendocrine tumors,mucinous tumors, differentiated teratomas, many prostatecarcinomas, lobular breast cancer, some renal andhepatocellular carcinomas, andmost bronchioloalveolar carcinomas. The relatively poor 18F-FDG uptake of these tumorscompromises the sensitivity of PET for the detection of tumorsites. 20
  21. 21.  The standardized uptake value (SUV) is a semi-quantitativemeasure of the tracer uptake in a region of interest thatnormalizes the lesion activity to the injected dose and bodyweight; SUV does not have a unit. Despite initial enthusiasm, it is generally accepted that SUVshould not be used to differentiate malignant from benignprocesses, and that the visual interpretation of PET studies byan experienced reader provides the highest accuracy. 21
  22. 22.  There are many factors influencing the calculation of SUV,such as the body weight and composition, the time betweentracer injection and image acquisition, the spatial resolution ofthe PET scanner, and the image reconstruction algorithm. Nonetheless, SUV may be useful as a measure to follow themetabolic activity of a tumor over time within the same patientand to compare different subjects within a research study underdefined conditions. For example, the SUV of an individualtumor can be measured before and at different time points aftertherapy, and any change can be used as an index oftherapeutic response. 22
  23. 23.  Research in PET radiochemistry has provided access tomany alternative tracers for oncology at the present time. Many of these tracers have been evaluated in bothpre clinical and clinical studies. Some have the ability to uniquely characterize specificaspects of tumour biology and, as a result, to offer severaldiagnostic advantages in comparison with 18F-FDG inparticular types of tumours. 23
  24. 24. 24
  25. 25.  Sensitivity describes how often the imaging test wouldgive a “positive result” in a patient with cancer (i.e., true-positive [TP] finding). A test with high sensitivity has a lownumber of false-negative results. Specificity is the frequency with which a test result isnegative if no disease is present, or the true-negative (TN)ratio. A highly specific test has a low frequency of false-positive results Accuracy is 100 * (TP + TN)/(TP + FP + TN + FN).A highly accurate test is one with a low prevalence offalse-positive and false-negative results. 25
  26. 26. PET Scan in Lung Cancer PET has an overall sensitivity of more than 90% and aspecificity of about 85% for diagnosing malignancy in primaryand metastatic lung lesions; the sensitivity of PET forbronchoalveolar lung cancer and carcinoid of the lung is about60%, and the specificity of PET for lung cancer is lower inareas with a high prevalence of granulomatous lung disease. It is expected that the use of PET for diagnosing malignancyin indeterminate lung nodules will continue to grow as morepatients are diagnosed with nodules on CT performed for otherindications or as a screening test. 26
  27. 27.  FDG-PET is useful in staging of lung cancer by detectingmediastinal nodal involvement PET has greater sensitivity andspecificity than CT, but it is still imperfect. Nodes that appearinvolved by PET or CT should be sampled for confirmation oftheir status when such information will lead to alterations inclinical management, particularly when deciding whether toconsider resection. FDG-PET has also been studied for evaluating the responseto pre-operative chemotherapy or chemo-radiation and fordistinguishing between viable tumor and fibrosis in patientswho have received RT or chemotherapy, or both, in assessinglocal disease control in patients treated non-operatively. 27
  28. 28.  PET is justified instead of a battery of other tests (e.g., bonescan, CT, MRI) to assess for distant metastases. PET is more sensitive (90% vs. 80%) and more specific(90% vs. 70%) than bone scan in detecting bone metastasesfrom NSCLC; PET has a sensitivity and specificity of greaterthan 90% in detecting adrenal metastases from NSCLC. BrainCT or MRI is still needed because PET cannot reliably detectbrain metastases because of physiologically intense brainuptake of FDG. For patients with stage IV tumors, PET may be able toindicate the most accessible site for biopsy. 28
  29. 29.  PET is also useful in restaging NSCLC.In particular, PET appears to be more sensitive than CT indifferentiating post-irradiation change from local recurrence,although differentiating these two entities remains a challenge.The post-irradiation change in the chest can remain intense onPET for up to several years. In differentiating local recurrencefrom post-irradiation change, the intensity of uptake and itsshape should be taken into account 29
  30. 30. PET Scan in Lymphoma Positron emission tomography (especially fused PET/CT) issuperior to conventional CT in staging of Hodgkin’s diseaseand non-Hodgkin’s lymphoma; however, there is no definiteevidence that PET changes the initial management oflymphoma patients. Nonetheless, because most recurrencesoccur at the sites of the primary disease, pre-treatment PETappears helpful in identifying recurrence. 30
  31. 31.  Hodgkin’s disease and high-grade NHL are mostly markedlyavid for FDG and almost always visible on PET, whereas low-grade NHL can be only mildly intense and, in rare cases,completely invisible on PET. Intense spleen uptake (i.e., more intense than the liver)before chemotherapy is a reliable indicator of its involvement,but spleen involvement by lymphoma cannot be excluded withnormal uptake. PET cannot be used to reliably evaluate bone marrowinvolvement. 31
  32. 32.  The most promising role of PET in lymphoma managementappears to be in therapy monitoring: early prediction ofresponse to chemotherapy (i.e., interim or midway PET) andevaluation of a residual mass for active lymphoma at thecompletion of chemotherapy (i.e., end-of-treatment PET). The decrease of uptake associated with effectivechemotherapy seen on interim PET precedes the anatomicchanges seen on CT by weeks to months. Overall, metabolicchanges on interim PET after one or a few cycles ofchemotherapy are reliable predictors of response, progression-free survival rates, and overall survival rates. 32
  33. 33.  End-of-treatment PET has proven impact in patient care.At the completion of chemotherapy, CT demonstrates aresidual mass at the initial site of disease in as many as 50%of patients. On the end-of-treatment PET, these patientsdemonstrate increased FDG uptake in the area of residuallymphoma in contrast to those without active lymphoma. Thepositive predictive value of residual uptake at the completion ofchemotherapy is more than 90%. In follow-up of patients in remission, PET is more sensitivethan CT in detecting recurrent disease. 33
  34. 34. PET Scan in Head & Neck Cancers In initial staging of head and neck tumors, PET has asensitivity and specificity of about 90% for nodal staging, andPET therefore is more sensitive and specific than CT or MRI. Aweakness of PET is its low sensitivity (30%) for nodal diseasein patients with disease in the neck at clinical stage N0. In addition to local staging, PET can detect synchronouscancers and distant metastases. In initial staging of head andneck cancers, a PET scan is overall most helpful in patientswith locally advanced disease because these patients have arisk of 10% or greater for distant disease. 34
  35. 35.  For restaging of head and neck tumors after radiationtherapy, PET is highly sensitive; however, the optimal time toperform PET is a matter of debate.There is a higher likelihood of false-positive findings when PETis performed earlier than 3 months after irradiation. For patients presenting with metastatic neck nodes withunknown primary PET is useful in the search for the originallesion. 35
  36. 36. PET Scan in Colorectal Cancers PET is highly sensitive in detecting distant hepaticand extra-hepatic metastases. Considering the higher sensitivity of PET in detectingdistant metastases and the introduction of intravenouscontrast media to the CT portion of fused PET/CT, it isconceivable that PET/CT will be increasingly employed inpre-operative staging of colorectal cancer; the contrast-enhanced CT portion of PET/CT can be used instead ofconventional CT or MRI for evaluation of anatomic resectabilityof liver metastases. 36
  37. 37.  PET plays an important role in restaging of colorectalcancer and is even more important now that it is known thattreatment of limited metastatic disease can be curative. PET can visualize the site of the local and distant diseasewhen recurrence is suspected based on the clinical findings,findings on other imaging modalities, or an increasingCEA level with sensitivity and specificity higher than 90% 37
  38. 38. PET Scan in Breast Cancer PET can increase the detectability of small primary breastcancers and may be especially useful in evaluating patientswith dense breast tissue. Its role in routine patient care isunder investigation. In evaluating the axillary lymph nodes, PET does not playany role because of its low sensitivity (60%) despite relativelyhigh specificity (80%). In contrast, PET is relatively sensitive(85%) and specific (90%), and it is superior to CT (sensitivity of54%, specificity of 85%) in evaluation of the internal mammarychain lymph node for metastases. 38
  39. 39.  The main role of PET in breast cancer lies in theinvestigation of distant metastases and response monitoring. Compared with CT, PET has a higher sensitivity (90% vs.40%) but lower specificity (80% vs. 95%) in detectingmetastatic disease. Overall, PET has the same sensitivity as bone scan indetecting bone metastases (both about 90%), but PET appearsto be somewhat more sensitive than bone scan for osteolyticlesions and somewhat less sensitive than bone scan forosteoblastic lesions. PET has a higher specificity than bonescan in detecting bone metastases (95% vs. 80%). 39
  40. 40.  In patients with advanced breast cancer undergoingneo-adjuvant chemotherapy, PET may differentiate respondersfrom non-responders as soon as the first cycle of therapy hasbeen completed. This may help improve patient managementby avoiding ineffective chemotherapy and supporting thedecision to continue dose-intensive pre-operativechemotherapy in responding patients. 40
  41. 41. In esophageal and gastric cancers, PET is useful to assess fordistant disease. PET is routinely used in the staging ofesophageal cancer, and it has the potential to be used formonitoring the effect of neo-adjuvant therapy.In ovarian, uterine, and cervical cancers, PET is used to assessfor recurrent disease. In cervical cancer, PET plays animportant role in nodal staging and can have a role inradiotherapy planning.In malignant melanoma, PET is used to evaluate the presenceof distant metastases. In sarcoma, the most intense areas onPET have usually the highest grade and should be consideredin planning the biopsy. 41
  42. 42. This is a very interesting caseof a 67 year old gentleman with threepulmonary nodules on CT scan. Hewas referred for PET/CT, whichshowed only one of the three noduleswas FDG avid.A subsequent biopsy of the FDG avidnodule showed adenocarcinoma.The surgeon and the patient decidedto resect all three nodules. Thepathology of the three nodulesshowed adenocarcinoma, a moreperipheral area of infarct fromtumor embolus and in the otherlung a benign hamartoma.In this particular case, PET/CTaccurately identified the malignantnodule from the other two benignnodules. 42
  43. 43. thank you 43