Indian Journal of Cancer Medknow Publications on behalf of Indian Cancer Society ISSN: 0019-509X EISSN: 1998-4774 Vol. 47, Num. 4, 2010, pp. 371-379

Indian Journal of Cancer, Vol. 47, No. 4, October-December, 2010, pp. 371-379

Symposium

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

S Basu¹, R Kumar², A Alavi³

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

Correspondence Address:
A Alavi
Nuclear Medicine Section, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA
USA
abass.alavi@uphs.upenn.edu

Code Number: cn10092

PMID: 21131748

DOI: 10.4103/0019-509X.73562

Abstract

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

Introduction

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

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

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 pannel] 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.

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.)

Tuberculosis

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].

Osteomyelitis

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].

Fever of Unknown Origin and Various Soft Tissue Infection

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].

Infection Associated with Prosthesis and other Orthopedic Devices

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].

Vascular Graft Evaluation for Infection

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].

Uptake in the Vascular Wall in Vasculitis and Atherosclerosis

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].

Inflammatory Bowel Disease

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].

Conclusion

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

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