1. Kh Taalab IMC Role of FDG PET In Characterization of Lung Diseases Cairo Chest 2014 Khalid Muhammad Taalab M.B,B.Ch., M.Sc., M.D. IAEA- Research Fellowship Nuclear Medicine International Medical Center

2. Indications: FDG PET CT in lung disease Cancer Infection & inflammation

3. Normal cells use glucose GLU FDG Glut 1 & 3 GLU CO 2 +H 2 0 FDG hexokinase FDG-6- phoshate GLU-6-phoshate

4. Cancer cells use much glucose GLU FDG Glut 1 & 3 GLUGLU-6-phoshate CO 2 +H 2 0 FDG FDG-6- phoshate Metabolic trapping (Warburg O. 1930, 129-169) * Also high amino acid and nucleic acid use

5. Fused PET + CTLow dose CT PET

6. Fused PET + CTCT PET Anato-metabolic imaging

7. Indications: PET in pulmonary disease Cancer @ –Pulmonary nodules –Staging (NSCLC) –Relaps and re-staging –Treatment monitoring –SCLC –Mesothelioma –[Radiation field planning] @ PET costs covered by US Medicare

8. Indications: PET in pulmonary disease Cancer @ –Pulmonary nodules –Staging (NSCLC) –Relaps and re-staging –Treatment monitoring –SCLC –Mesothelioma –[Radiation field planning] Infection & inflammation* –Localisation and monitoring of activity: –Sarcoidosis –AIDS (opportunistic infections and malignancy) –Fever of unknown origin –Lung abscess –Tuberculosis, Actinomycosis, Histoplasmosis, Invasive aspergillosis –Vasculitis (Wegener, Takayasu..) –Radiation induced inflammation * = Sem Nucl Med 2002 ;32: 293-321 @ PET costs covered by US Medicare

9. Case: 57 y-o-m with COPD 9 mm nodule found on high- resolution CT 18 F-FDG PET

10. transaxial coronal saggital attenuation corrected RH - PET / jm (ap) Diagnosis and staging (PET suggests T1 N0 M0) Case: 57 y-o-m with COPD

11. FDG PET for extrathoracic metastasis 40% with NSCLC have distant metastases at presentation, most often in the adrenal glands, bones, liver, or brain [Ann Thorac Surg 1996;62:246–250]. Adrenal glands: 10% of NSCL have enlarged adrenal glands on CT, 2/3 being benign. PET has high sensitivity (>92%) and specificity (80%–100%) -> reduces number of unnecessary adrenal biopsies. Bone: Bone scintigraphy good sensitivity (90%), low specificity (±60%), PET good sensitivity (90%), but higher specificity (98%) and accuracy (96%). Liver: US and/or CT remain the standard imaging techniques for the liver. No good comparisons studies. Additional diagnostic information by PET combined with CT, in the differentiation of hepatic lesions that are indeterminate on conventional imaging. Brain: PET low sensitivity (60%) not suited for the detection of brain metastases. The Oncologist 2004; 9 (6): 633-43

12. ”PET/CT will improve staging in 20- 40 % of lung cancer patients” Lardinois D et al. N Engl J Med 2003; 348: 2500-7 PET/CT in lung cancer Cerfolio RJ et al. Ann Thorac Surg 2004; 78: 1017–23 A randomised study in progress in Copenhagen

13. Bone metastasis with normal CT

14. Impact of PET in lung cancer PET changes stage in 35% of patients (N=894, 16 studies) – Usually the PET stage is higher than with usual work-up incl. CT Due to local (N2 eller N3) metastasis or extra-pulmonary metastasis – ie. operation is unnecessary – change in therapy to chemotherapy and / or radiation treatment Semin Nucl Med 2002, 32:240-71 PET is cost effective in lung cancer – Both for diagnosis of single pulmonary nodules and for Staging – References: (Gambhir J Clin Oncol 1998; 16: 2113-2125) (Dietlein Eur J Nucl Med 2000; 27: 1441-56) (Gould ARRDCCM 2001) (Plus study)

15. Increased FDG-PET uptake can be seen in benign mediastinal adenopathies (Z) Granulomatosis and silicosis (Inflammation) –Sarcoidosis –Anthrasilicosis Infections –Histoplasmosis, –Tuberculosis (and M avium intracellulare) –Actinomycosis, etc. Benign neoplasm (-thymoma, teratoma, swannoma) Iatrogenic disorders (Radiation related changes) (Z) Yet, only a minority with these conditions have a high FDG uptake Sem Nucl Med 2002;32(4): 293-321 Case stories

16. TB in a 58-year-old man. (A) chest radiograph shows two nodules (b) coronal FDG PET scan shows increased uptake (solid arrow) in the left upper lobe nodules (SUV 4). Radiology 2000 6:117-21 FDG PET in active tuberculosis

17. Sarcoidosis Milman N, Mortensen J, Sloth C. Respiration. 2003;70:408-13. Before treatment: After inhaled steroid: After prednisolone: Localisation of activity in- and outside lungs: Monitoring:

18. Newer indications for PET in lung cancer Prognostic information from SUV Evaluation of treatment effect -> PET/CT for planning of radiation field Staging and monitoring SCLC -> Staging and diagnosis of Mesothelioma FDG PET for: Guiding of biopsy Staging (extrathoracic or contralateral metastasis) J Nucl Med. 1999 Aug;40(8):1241-5. Semin Oncol. 2002 Feb;29(1):26-35.

19. Axial FDG-PET image shows intense uptake (arrow) in the left upper lobe suggesting a malignant condition with a maximum standardized uptake value of 4.3. The pathologic examination reveals tuberculoma. Another lesion showing high FDG uptake (arrowhead) is a pulmonary artery.

20. Tuberculous Lymphadenopathy: Coronal FDG-PET scan shows high uptake in the same area (arrow).

21. Cryptococcosis Cryptococcosis Contrast-enhanced CT scan shows a cavitary nodule in the left lower lobe (arrowed ). Transverse section of a whole body PET image shows increased uptake (arrowed) in the left lower lobe and a standardized uptake value of 2.6. The lesion is a round mass-like lesion unlike the CT findings due to respiration artifact.

22. Lung abscess: Axial contrast enhanced CT scans show a consolidation with air density in the right upper lobe (black arrow). Multiple conglomerated mediastinal lymph node enlargements are also noted (white arrow). Lung abscess: Axial contrast enhanced CT scans show a consolidation with air density in the right upper lobe (black arrow). Multiple conglomerated mediastinal lymph node enlargements are also noted (white arrow). Coronal FDG-PET image shows high uptake (arrows) in the right upper lobe. High uptake in the left hilar lymph node (arrowhead) is also noted. Malignancy is suspected in PET scan. Per-cutaneous needle biopsy reveals a lung abscess. Coronal FDG-PET image shows high uptake (arrows) in the right upper lobe. High uptake in the left hilar lymph node (arrowhead) is also noted. Malignancy is suspected in PET scan. Per-cutaneous needle biopsy reveals a lung abscess.

23. Radiation Fibrosis Radiation Fibrosis Axial CT scan shows consolidation in the left lower lobe, suggesting lung cancer recurrence. Axial CT scan shows consolidation in the left lower lobe, suggesting lung cancer recurrence. Axial PET image shows increased uptake in the left lower lobe (arrow) which was mistaken for lung cancer recurrence. Axial PET image shows increased uptake in the left lower lobe (arrow) which was mistaken for lung cancer recurrence.

24. Pneumoconiosis with Combined Massive Fibrosis Pneumoconiosis with Combined Massive Fibrosis Progressive massive fibrosis in a 58-year-old male. Coronal FDG-PET image shows increased uptake in right upper lobe (arrow) and the standardized uptake value max. of 6.4. Progressive massive fibrosis in a 58-year-old male. Coronal FDG-PET image shows increased uptake in right upper lobe (arrow) and the standardized uptake value max. of 6.4.

25. Bronchiolo-alveolar Carcinoma (BAC) Bronchiolo-alveolar Carcinoma (BAC) Axial chest CT images show a low attenuating mass in the left upper lobe. Axial chest CT images show a low attenuating mass in the left upper lobe.

26. FDG-PET also shows a hyper-metabolic lesion with a maximum standardized uptake value of 3.8 in the left upper lobe. FDG-PET also shows a hyper-metabolic lesion with a maximum standardized uptake value of 3.8 in the left upper lobe.

27. Another area of ground-glass opacity is noted in the right lower lobe. Another area of ground-glass opacity is noted in the right lower lobe. FDG-PET shows no abnormal uptake in this area. FDG-PET shows no abnormal uptake in this area. Both the left upper and right lower lobe lesions were bronchioloalveolar carcinomas, mucinous type. In the same patient, FDG uptake for each of the lung lesions was different, and the amount mucin in mass may have been the major cause of this difference. Both the left upper and right lower lobe lesions were bronchioloalveolar carcinomas, mucinous type. In the same patient, FDG uptake for each of the lung lesions was different, and the amount mucin in mass may have been the major cause of this difference.

28. Metastatic Lung Nodule of Extrapulmonary Neoplasm Metastatic Lung Nodule of Extrapulmonary Neoplasm FDG-PET fusion CT shows a nodular lesion in the right lower lung without increased FDG uptake (arrow). FDG-PET fusion CT shows a nodular lesion in the right lower lung without increased FDG uptake (arrow). Mucinous adeno-carcinomas of gastrointestinal origin can also show false negative findings in PET scans. Mucinous adeno-carcinomas of gastrointestinal origin can also show false negative findings in PET scans.

29. Axial CT scan of lung window setting shows a lung nodule metastasis from renal cell carcinoma in the right middle lobe (arrow). Axial CT scan of lung window setting shows a lung nodule metastasis from renal cell carcinoma in the right middle lobe (arrow). A selected transverse section of whole body-PET image shows no demonstrable uptake in the right lung. A selected transverse section of whole body-PET image shows no demonstrable uptake in the right lung.

30. Help from a PET-scan A positive PET focus indicates malignancy but needs histological proof (to avoid false positive) PET or PET/CT guided biopsy possible A negative PET focus indicates benignancy –A solitary pulmonary nodule is either benign or very slowly growing cancer (no or CT control 6-12 months for growth) –Staging, no metastasis found, refer to operation.

31. Conclusion Single Pulmonary Nodules –Differentiate between benign/malignant indeterminate SPN if biopsy is difficult / nondiagnostic confirm benignity with CT follow-up –the uptake predicts prognosis (high metabolism -> bad prognosis) Staging Regional (N) and distant (M) metastases: –Addition of PET improves conventional staging (CT+US+ bone scintigraphy) –PET changes stage and treatment in ~35 % of patients Detects unexpected distant metastases in ~14 % Exclusion of malignancy in ~5 % (can be operated) Usually a higher stage is found Avoids unneccesary thoracotomy (in 10-20 %) -Mediastinoscopy can be avoided if PET + CT are normal (in non-central tumors) -Other indications: -Restaging and treatment monitoring, radiation field planning, SCLC, Mesothelioma -Localisation & monitoring of infections & inflammatory disorders

32. INTERNATIONAL MEDICAL CENTER