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  In this article
 »  Abstract
 »  Introduction
 »  Molecular Basis ...
 »  Sarcoidosis
 »  Tuberculosis
 »  Osteomyelitis
 »  Fever of Unknown...
 »  Infection Associ...
 »  Vascular Graft E...
 »  Uptake in the Va...
 »  Inflammatory Bow...
 »  Conclusion
 »  References
 »  Article Figures

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Table of Contents
SYMPOSIUM
Year : 2010  |  Volume : 47  |  Issue : 4  |  Page : 371-379
 

PET and PET-CT imaging in infection and inflammation: Its critical role in assessing complications related to therapeutic interventions in patients with cancer


1 Radiation Medicine Centre (BARC), Tata Memorial Hospital Annexe, Parel, Mumbai, India
2 Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi - 110 029, India
3 Nuclear Medicine Section, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

Date of Web Publication4-Dec-2010

Correspondence Address:
A Alavi
Nuclear Medicine Section, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.73562

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 » Abstract 

Over the past decade, there has been an increasing evidence of false-positive FDG uptake in several infectious diseases and aseptic inflammatory processes. With the widespread application of FDG-PET imaging in oncology, the interpreting physicians have come across these conditions frequently leading to false-positive diagnosis. Such conditions can coexist with metastatic lesions in patients with cancer, and hence, early and accurate diagnosis or exclusion of infection and inflammation is of utmost importance for the optimal management of these patients. Also, this powerful imaging modality can play an invaluable role for the appropriate management of these complicated benign conditions. The present communication on this non-oncological application of FDG is intended as an educative primer for practicing oncologists on this very important aspect of PET-CT imaging with an ultimate aim for bettering patient management.


Keywords: PET, FDG, PET-CT, Infection, Inflammation, Tuberculosis, sarcoidosis, vasculitis, pyrexia of unknown origin, vascular graft infection


How to cite this article:
Basu S, Kumar R, Alavi A. PET and PET-CT imaging in infection and inflammation: Its critical role in assessing complications related to therapeutic interventions in patients with cancer. Indian J Cancer 2010;47:371-9

How to cite this URL:
Basu S, Kumar R, Alavi A. PET and PET-CT imaging in infection and inflammation: Its critical role in assessing complications related to therapeutic interventions in patients with cancer. Indian J Cancer [serial online] 2010 [cited 2018 Dec 10];47:371-9. Available from: http://www.indianjcancer.com/text.asp?2010/47/4/371/73562



 » Introduction Top


From serendipitous observations made as the source of non-specific FDG accumulation in the context of malignancies, recent years have witnessed rapid strides in the potential applications of FDG-PET in several infectious diseases and aseptic inflammatory processes, and the literature on this issue is rapidly evolving. [1],[2],[3],[4],[5] Concerns have been raised, at the same time, with regard to the specificity of this high resolution molecular imaging technique in patients with cancer where such false positives can lead to serious consequences. Hence, it is imperative, both from the perspectives of the interpreting nuclear medicine physician as well as the oncologists, to appreciate the PET findings in these conditions, the realization of which is of great importance for the optimal management and decision making in these patients. The treatise, thus, is presented in the form of a pictorial review with case vignettes upholding the varying etiopathologies responsible for the FDG uptake.


 » Molecular Basis of FDG Uptake in Infection and Inflammation Top


While several molecular mechanisms have been proposed as the basis for FDG uptake in the inflammatory cells, overexpression of GLUT-1 subtype in the stimulated macrophages, neutrophils, and lymphocytes is considered the most likely underlying biological phenomenon responsible for this observation. The activated inflammatory cells accumulate FDG with high concentration depending upon the degree of stimulation that is a function of inflammatory activity at the respective site.


 » Sarcoidosis Top


Sarcoidosis is a multisystem granulomatous inflammatory disease characterized by non-caseating granulomas. FDG uptake based upon disease activity is observed, which can be of substantial benefit in monitoring treatment efficacy. Assessment of disease activity in patients with sarcoidosis is critical to determine whether corticosteroid therapy is efficacious and whether the dose of the drug should be modified.

FDG-PET [Figure 1]: [upper panel] showed multiple abnormal foci of FDG uptake in the both sided neck nodes, mediastinal and axillary nodes, liver, spleen, thyroid and multiple abdominal (paraaortic and inguinal nodes). The biopsy of the inguinal nodes was confirmatory of sarcoidosis. He had a history of hypothyroidism, which is frequently associated in this disorder and is predicted to be due to association of autoimmunity that is very important in the pathogenesis of thyroid disease in this population. The patient was prescribed oral corticosteroid and was referred for reassessment of disease status following 6 weeks of initiation of therapy. The FDG-PET this time [Figure 1]: [lower panel] showed remarkable improvement of the disease status with near total resolution FDG hypermetabolism at the involved sites.
Figure 1: A 52-year-old male, who presented with cervical lymphadenopathy and initially diagnosed to have tuberculosis and was treated with anti-tubercular drugs for 1 year without benefit, was referred for further evaluation. He was considered for re-biopsy for a definitive diagnosis. At the same time, he was referred for FDG-PET study to evaluate the overall disease status. FDG-PET (Fig 1: upper panel) showed multiple abnormal foci of FDG uptake in the both sided neck nodes, mediastinal and axillary nodes, liver, spleen, thyroid and multiple abdominal (paraaortic and inguinal nodes). The biopsy of the inguinal nodes was confirmatory of sarcoidosis. He had history of hypothyroidism, which is frequently associated in this disorder and is predicted to be due to association of autoimmunity that is very important in the pathogenesis of thyroid disease in this population. The patient was prescribed oral corticosteroid and was referred for reassessment of disease status following 6 weeks of initiation of therapy. The FDG-PET this time (Fig 1: lower panel) showed remarkable improvement of the disease status with near total resolution FDG hypermetabolism at the involved sites. (Reproduced from Basu et al.[1] with permission from Lippincott Williams and Wilkins)

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Note: The present case underscores the value of FDG-PET imaging in whole body monitoring of early response to therapy in patients of sarcoidosis (particularly those with extensive disease) and indicates the promise of this powerful molecular imaging technique in managing this multisystem disorder. (Reproduced from Basu et al. [1] with permission from Lippincott Williams and Wilkins)

A 43-year-old woman with newly diagnosed invasive ductal right breast cancer underwent a FDG-PET examination for preoperative staging. The FDG-PET study [Figure 2] revealed multiple sites of increased uptake in bilateral hilar and mediastinal regions consistent with an FDG avid metabolically active process; the pattern of activity is not typical for breast cancer metastases and can be caused by conditions like lymphoma or sarcoidosis. Histopathological examination of these lesions obtained by mediastinoscopy demonstrated non-caseating granulomas without malignant cells noted due to sarcoidosis. (Reproduced from Yu et al.[2] with permission from Elsevier Inc.)
Figure 2: Sarcoidosis in Diagnosed Patient of Invasive Ductal Carcinoma. A 43-year-old woman with newly diagnosed invasive ductal right breast cancer underwent a FDG-PET examination for preoperative staging. The FDG-PET study [Figure 2] revealed multiple sites of increased uptake in bilateral hilar and mediastinal regions consistent with an FDG avid metabolically active process; the pattern of activity is not typical for breast cancer metastases and can be caused by conditions like lymphoma or sarcoidosis. Histopathological examination of these lesions obtained by mediastinoscopy demonstrated non-caseating granulomas without malignant cells noted due to sarcoidosis. (Reproduced from Yu et al.[2] with permission from Elsevier Inc.)

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 » Tuberculosis Top


By now, it is evident that tuberculous lesion can demonstrate variable FDG uptake determined by the inflammatory activity. FDG concentrating bilateral hilar and mediastinal foci associated with this diaease have been a source of concern in the current PET practice in oncological setting benign or malignant pathologies draws attention of the readers to a very important and practically relevant issue of current PET practice in oncological setting. This has a geographical relevance and is of major concern in the Asian countries including India, where tuberculosis has a high prevalence, and hence, the need for educating the physicians who are actively involved in the interpretation of PET images to obviate errors in this confounding situation can hardly be overemphasized [Figure 3], [Figure 4], [Figure 5].
Figure 3: Tubercular inflammatory lesion left apex showing FDG uptake (Reprinted with permission from American Society for Microbiology from Kumar et al.[3])

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Figure 4: Pre- (upper panel) and post-treatment (lower panel) FDG-PET in a proven case of tuberculosis (Reprinted with permission from American Society for Microbiology from Kumar et al.[3])

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Figure 5: Left renal cell carcinoma, Post nephrectomy, post chemotherapy. PET-CT scan was done for restaging, which showed mediastinal lymphdenopathy with intense FDG uptake that was suspicious of metastases. However, FNAC demonstrated findings of tuberculosis

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 » Osteomyelitis Top


Several studies and reports have documented avid FDG uptake in osteomyelitis and the important role of FDG-PET in diagnosing patients with chronic osteomyelitis. It is expected that FDG-PET imaging will be used routinely in the near future to determine the presence or absence of an infectious focus, to monitor response to antimicrobial treatment, and to develop certain criteria for deciding when the treatment can be safely stopped [Figure 6], [Figure 7].
Figure 6: A 48-year-old man with back pain: Whole body FDG-PET images reveal 2 foci of increased uptake at the level of T9-T11 as clearly shown on sagittal images. These sites were proven to represent osteomyelitis. (Reproduced with permission from Elsevier Inc. for Zhuang et al.[4])

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Figure 7: Avid FDG uptake in the sinus tract connecting soft tissue abscess with bone in a patient of proven Chronic Osteomyelitis. (Reprinted with permission from American Society for Microbiology from Kumar et al.[3])

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 » Fever of Unknown Origin and Various Soft Tissue Infection Top


Fever of unknown origin (FUO) is a clinical challenge especially in the elderly and may become an accepted indication for 18 F-FDG-PET in clinical practice. The nonspecificity of FDG is of great value in evaluating patients with FUO because it accumulates in infections, malignancies, and inflammatory diseases, which are the three major etiopathologies of FUO [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14].
Figure 8: A 44-year-old man after heart transplant presented with FUO and inconclusive radiologic studies, including CT. Coronal PET images demonstrates a focus of increased FDG activity in the aortopulmonary window and represents the source of infection. The patient completely recovered following drainage of the infected site in the mediastenum (Reproduced with permission from Elsevier Inc. for Basu et al.[5])

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Figure 9: Avid FDG uptake in the focus of infection in a patient of proven malignant otitis externa (Reproduced with permission from Elsevier Inc. for Zhuang et al.[4]).

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Figure 10: Patient of HD underwent for PET-CT for staging. Axial sections of CT, PET, and PET-CT showed increased FDG uptake in multiple right cervical lymph nodes. Follow-up PET-CT scan showed resolution of primary lesions, however diffuse increased FDG uptake was noted in contralateral parotid gland. FNAC of the same confirmed the diagnosis of parotitis.

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Figure 11: The attenuation-corrected FDG-PET images in the transverse (a) and sagittal (b) slices show a pleural-based lesion with intense FDG activity in the left lung base posteromedially (thin arrow). This was due to a fungal infection. (Reproduced with permission from Elsevier Inc. for Alavi et al.[6])

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Figure 12: This attenuation-corrected coronal FDG-PET image shows a large lesion with intense and heterogeneous FDG uptake in the left upper lobe (thin arrow). The final diagnosis was asperglllosls. (Reproduced with permission from Elsevier Inc. for Alavi et al.[6])

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Figure 13: Pre- and post treatment FDG-PET in a proven case of Pneumonia (Reprinted with permission from American Society for Microbiology from Kumar et al.[3])

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Figure 14: Known patient of Non Hodgkin's lymphoma who underwent for PET-CT for restaging, coronal and axial section of CT showed parenchymal lesion in left lung apex. PET showed increased FDG uptake that was subsequently proven to be active inflammatory lesion

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 » Infection Associated with Prosthesis and other Orthopedic Devices Top


The differentiation between infection and prosthetic loosening without infection is a major challenge for orthopedic surgeons. While prosthesis revision is often successful and is not associated with major complications for aseptic loosening alone, the presence of superimposed infection requires intensive treatment before surgical revision is undertaken. Abnormal FDG uptake along the bone prosthesis interface in the middle portion of the shaft of the prosthesis is the most reliable indicator of periprosthetic infection as it is well known that nonspecific FDG accumulation may be present around head and neck portion of the prosthesis for several months (and possibly years) after surgery [Figure 15], [Figure 16], [Figure 17].
Figure 15: Classical FDG-PET finding in a patient with infection of the Hip Prosthesis (Reprinted with permission from American Society for Microbiology from Kumar et al.[3])

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Figure 16: 82-year-old woman who received right hip replacement 13 years ago and who presented with hip pain. PET images (MIP) demonstrated increased FDG uptake around the proximal portion of the prosthesis, subcutaneous tissue, and muscles of the right anterior thigh and pelvis. FDG uptake is also noted in the right posterolateral abdominal wall muscles, consistent with extensive infection involving the right proximal prosthesis extending into the right flank. PET/CT images demonstrate sites of abnormal uptake in the psoas muscle which extends to the flank. On the basis of the PET/CT findings, the abscess was drained transcutaneously with successful outcome. (Reproduced with permission from Elsevier Inc. for Basu et al.[5])

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Figure 17: Shown is a 43-year-old man with a history of tibia-fibula fracture requiring external fixator. Coronal PET images demonstrate intensively increased FDG uptake in the distal tibial region that extends to the skin, representing a fistula tract. Surgical and histopathological examinations confirmed osteomyelitis. (Reproduced with permission from Elsevier Inc. for Basu et al.[5]).

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 » Vascular Graft Evaluation for Infection Top


FDG-PET is a valuable tool in the evaluation of possible infection of vascular grafts. FDG-PET is able to detect vascular graft infection even when CT results are negative. This early diagnosis can aid in rapid surgical intervention with graft removal and required bypass. Based upon the initial encouraging results, larger controlled studies have been undertaken to evaluate the utility of FDG-PET in the diagnosis of prosthetic aortic graft infection [Figure 18].
Figure 18 (a-b): While the CT scan did show evidence of retroperitoneal stranding (arrows), no definitive evidence of aortic graft infection such as ectopic air, perigraft abscess, or pseudoaneurysm was evident. Figure 18 (c). PET scan revealed abnormal FDG uptake in the area of the aorta corresponding to the graft (arrow). (Reproduced with permissions from the Sage Publications for Krupnik et al.[7])
Figure 18. A fistulous connection between the jejunum and the aortic graft was evident at laparotomy. Arrows point to a probe placed through the fistula as seen from the luminal (d) and serosal side (e) (Reproduced with permissions from the Sage Publications for Krupnik et al.[7])


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 » Uptake in the Vascular Wall in Vasculitis and Atherosclerosis Top


FDG-PET has the potential to be added to the imaging armamentarium as a functional technique for scanning and detection of metabolically active processes along large- and medium-sized arteries. It has been reported to be useful in the diagnosis and treatment of patients with vasculitis by several investigators. FDG-PET/CT has also been considered by several authorities to hold great promise for assessing atherosclerosis in large arteries. Vascular FDG uptake also has been linked to cardiovascular events by several reports [Figure 19], [Figure 20].
Figure 19: In this 72-year-old woman, the initial FDG-PET image (a) established the diagnosis of vasculitis by demonstrating intense uptake in the aorta and the subclavian arteries while a follow-up PET image after steroid therapy (b) revealed complete disappearance of the abnormalities noted on the initial scan. (Reproduced from Otsuka et al. with permission from The Journal of Medical Investigation.[8])

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Figure 20: FDG-PET/CT scan of a 69-year-old man with lung cancer. Images include CT on the left, PET in the middle, and fused PET/CT on the right. There is intense uptake of FDG in the wall of the descending thoracic aorta, often noted in patients with atherosclerosis (Reproduced with permission from Elsevier Inc. for Basu et al.[9])

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 » Inflammatory Bowel Disease Top


FDG-PET provides an objective means to noninvasively assess the severity of bowel inflammation in IBD, and hence, can be valuable in guiding therapy in inflammatory bowel disease by depicting inflammation in the whole bowel with high sensitivity and accuracy in a single examination [Figure 21].
Figure 21: FDG-PET/CT images show significant uptake in the distal ileum, which extends to the cecal region, which is mildly active (long arrow), clearly demonstrating the high sensitivity of this technique for detection of regional inflammation. Interestingly, there is serendipitous finding of FDG-avid right lower lobe bronchopneumonia (short arrow), which became symptomatic the day after the PET/CT study was acquired (Reproduced from Basu et al. with permission from Elsevier Inc.[10]).

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 » Conclusion Top


With the increasing application of FDG-PET imaging, there has been an evolving appreciation of its uptake in a wide range of infection and inflammatory disorders. The knowledge of this is of great importance as such false positives can lead to serious consequences. The PET-CT interpreting physicians as well as the clinical oncologists should be well aware to obviate these potential sources of error. At the same time, though examined in a relatively less number of studies compared to cancer, all have demonstrated that this molecular imaging modality holds great potential in evaluating disease activity in this group of disorders, and hence, can be of significant value in managing these benign but complicated disorders. [10]

 
 » References Top

1.Basu S, Asopa RV, Baghel NS. Early documentation of therapeutic response at 6 weeks following corticosteroid therapy in extensive sarcoidosis: Promise of FDG-PET. Clin Nucl Med 2009;34:689-90.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Yu JQ, Zhuang H, Mavi A, Alavi A. Evaluating the role of flurodeoxyglucose PET imaging in the management of patients with sarcoidosis. PET Clin 2006;1:141-52.  Back to cited text no. 2
    
3.Kumar R, Basu S, Torigian D, Anand V, Zhuang H, Alavi A. Role of modern imaging techniques for diagnosis of infection in the era of 18 F-fluorodeoxyglucose positron emission tomography. Clin Microbiol Rev 2008;21:209-24.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Zhuang H, Alavi A. 18-fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin Nucl Med 2002;32:47-59.  Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5.Basu S, Chryssikos T, Moghadam-Kia S, Zhuang H, Torigian DA, Alavi A. Positron emission tomography as a diagnostic tool in infection: Present role and future possibilities. Semin Nucl Med 2009;39:36-51.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Alavi A, Gupta N, Alberini JL, Hickeson M, Adam LE, Bhargava P, et al. Positron emission tomography imaging in nonmalignant thoracic disorders. Semin Nucl Med 2002;32:293-321.  Back to cited text no. 6
[PUBMED]    
7.Krupnick AS, Lombardi JV, Engels FH, Kreisel D, Zhuang H, Alavi A, et al. 18-fluorodeoxyglucose positron emission tomography as a novel imaging tool for the diagnosis of aortoenteric fistula and aortic graft infection: A case report. Vasc Endovascular Surg 2003;37:363-6.  Back to cited text no. 7
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8.Otsuka H, Morita N, Yamashita K, Nishitani H. FDG-PET/CT for diagnosis and follow-up of vasculitis. J Med Invest 2007;54:345-9.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Basu S, Zhuang H, Torigian DA, Rosenbaum J, Chen W, Alavi A. Functional imaging of inflammatory diseases using nuclear medicine techniques. Semin Nucl Med 2009;39:124-45.  Back to cited text no. 9
[PUBMED]  [FULLTEXT]  
10.Basu S, Torigian D, Alavi A. The role of modern molecular imaging techniques in gastroenterology. Gastroenterology 2008;135:1055-61.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20], [Figure 21]

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