**6.1 F-18 FDG: Pharmacological and physiochemical characteristics**

Fluorine 18 (F-18) Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) has been extensively used for imaging malignant processes, however, it is also now an established agent for imaging benign processes such as infection, inflammation and

suspected. In another recent study (Graute V et al., 2010) concluded that SPECT/CT substantially improves the utility of imaging with Tc-99m labelled anti-granulocyte antibodies for diagnosis and localization of suspected joint infections and provide information on the extent of the infection. We have found that SPECT/CT imaging not only helps anatomical localization of the infectious site but also provides lesion characterization

Fig. 10. A 25-year old female referred for evaluation of osteomyelitis in the left middle finger. Tc-99m MDP bone scan show hyperaemia, increased pool activity and intense linear increased tracer uptake in the left 3rd proximal phalanx extending up to the mid of middle phalanx. Tc-99m Sulesomab images show increased uptake at the same site confirming osteomyelitis. Further correlative SPECT/CT images show evident cortical distortion with

Fluorine 18 (F-18) Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) has been extensively used for imaging malignant processes, however, it is also now an established agent for imaging benign processes such as infection, inflammation and

**6. F-18 fluorodeoxyglucose positron emission tomography 6.1 F-18 FDG: Pharmacological and physiochemical characteristics** 

low attenuation changes.

and extent of involvement of the infectious process (Figure 10).

granulomatous disease. Increased F-18 FDG uptake in these tissues is attributed to the increased glucose consumption through the hexose monophosphate shunt, which is the main energy source in chemotaxis and phagocytosis. The respiratory burst or the phagocytes activation results in increased F-18 FDG uptake. Marked F-18 FDG uptake is seen in neutrophils during acute phase of inflammation while during the chronic phase it is the macrophages and polymorphonuclear leukocytes that take up the tracer. Therefore, in cases of sterile inflammation it is mainly the neutrophils and macrophages that take up F-18 FDG. The mechanism of F-18 FDG uptake in infectious and inflammatory process is the same as in malignancy with metabolic trapping of the F-18 FDG-6-phosphate that cannot be further metabolised as it is not a substrate for the glucose 6-phosphatase isomerase enzyme. However, as the level of glucose 6-phosphatase remains the same in inflammatory cells as opposed to tumour cells where they are decreased, the F-18 FDG washes out from the inflammatory cells in due course. Further the numbers of GLUT (glucose transporter receptors) are less in inflammatory cells when compared with tumour cells.

The normal distribution of F-18 FDG includes the brain, myocardium, and the genitourinary system with variable uptake seen in the stomach, bowel and the bone marrow. Increase F-18 FDG activity can be seen in the spleen in patients with infection and presumably reflects the increased glucose usage by spleen in the setting of an infectious process.

#### **6.2 F-18 FDG PET: Imaging protocols and pre-requisites**

The patients are advised to fast for several hours before imaging. This reduces the F-18 FDG uptake in normal tissues. Moreover, it reduces the competition for glucose transporters. The physical activity of the patient is limited prior to injection and this reduces the F-18 FDG uptake in the striated muscles. Some centers also administer benzodiazepines 30-60 minutes prior to injection to reduce the brown fat and muscle uptake. Patient is routinely injected 370-550 MBq of F-18 FDG intravenously and laid to rest in a comfortable bed. Imaging is usually done at 60 minutes post injection, however, some centers may extend the uptake period to 90 minutes or may acquire images twice at different times (dual point) particularly in cases of granulomatous processes such as tuberculosis. Whole body imaging is preferred in cases where a focus of infection is to be investigated. F-18 is cyclotron produced radioisotope. The physical half-life of F-18 is 110 minutes. The principal gamma photons produced are of 511 KeV energy generated by positron emission.

#### **6.3 F-18 FDG PET: Clinical utilities and applications**

The indications for F-18 FDG PET for imaging infection are not different from those discussed previously, however, in particular investigation for the site of infection or ascertaining the cause in FUO, vasculitis, HIV-AIDS, infected prostheses, as well as osteomyelitis, diabetic foot infections, sarcoidosis and tuberculosis have been studied.

In case of FUO, the sensitivity and specificity of F-18 FDG PET has been observed to be 84- 93% and 86-90% respectively. In most studies, it has helped in the management of about 35- 37% cases. The reported PPV is 87% and the NPV 95%. Negative F-18 FDG PET makes it very unlikely that a morphologic origin of the fever will be identified. Infective endocarditis that can be a source of FUO has also been studied with F-18 FDG PET.

F-18 FDG accumulation has been observed in certain conditions resulting in vasculitis. These include giant cell arteritis, Takayasu arteritis, polymyalgia rheumatica, aortitis/periaortitis, infectious vasculitis and unspecified large vessel vasculitis. Inflammation of the

Radionuclide Infection Imaging: Conventional to Hybrid 91

infections in AIDS patients. Most commonly the central nervous system is affected. F-18 FDG has been reported to be superior and more accurate than MRI in differentiating CNS lymphoma from conditions such as toxoplasmosis, progressive multi-focal leukoencephalopathy and syphilis. Further on quantitative assessment it has been shown that the standardized uptake values of toxoplasmosis are significantly lower than

F-18 FDG PET has been used extensively to evaluate painful lower limb joint prostheses. It has a limited significance especially when distinguishing infected joint prosthesis from aseptic prosthetic loosening. As inflammation is part of both the conditions, there is increased F-18 FDG peri-prosthetic accumulation observed in both. F-18 FDG PET is considered highly sensitive for evaluation of chronic osteomyelitis. Unlike bone scintigraphy F-18 FDG uptake normalizes in less than 2-3 months following treatment, thereby, reducing the false positive scans seen when osteomyelitis is suspected in complicated fractures. F-18 FDG PET has also been used with variable utility in diabetic foot infections, sarcoidosis, tuberculosis, organ transplantation and inflammatory bowel disease. In case of sarcoidosis the imaging findings are similar to those seen and discussed with Ga-67 scintigraphy. Further F-18 FDG PET can detect metastatic infectious foci with high

Hybrid PET/CT systems in fact gained more popularity than the SPECT/CT systems and PET imaging is synonymously used for PET/CT imaging. The incorporation of anatomical data fused with the functional PET images results in accurate localization of the abnormalities and moreover detailed characterization of the lesions can be ascertained. In our experience PET/CT imaging for infectious process has limited utility, primarily in cases of FUO, vasculitis, malignant otitis externa and assessment of chronic osteomyelitis. However, as more evidence based data surface, this modality may prove to be an important

Radiograph or plain films are almost always the initial imaging study for diagnosing and assessing osteomyelitis. Finding on plain films to suggest or support infectious process include periosteal elevation or thickening, cortical thickening, irregularity with loss of trabecular architecture, sclerosis, osteolysis, and new bone formation. It is however important to note that these changes may not be evident at least until 5-7 days in children and 10-14 days in adults. Plain films show lytic changes only after at least 50%-75% of the

Ultra-sonography is mostly utilized in evaluation and diagnosing of fluid collections, involvement of the periosteum, along with assessing surrounding soft tissue abnormalities. It may provide guidance for diagnostic or therapeutic aspirations, subsequent drainage

Anatomic imaging modalities including CT and MR imaging provide excellent structural resolution for the detection and characterization of infectious or inflammatory conditions. These provide a high-quality assessment of infection related structural abnormalities. However, the limitation is that these techniques rely solely on structural changes and,

method in detection and management of a number of infective conditions.

**7. Brief considerations and limitations regarding anatomic imaging** 

lymphoma with virtually no overlap.

sensitivity even if other imaging is negative.

**6.4 F-18 FDG PET: Hybrid PET/CT imaging** 

**modalities** 

bone matrix is destroyed.

and/or tissue biopsy.

vessel walls cannot be detected in the early phase on conventional anatomical imaging. F-18 FDG assists in early diagnosis, assessing the extent of the disease and has also been found superior to MRI in depicting disease activity and treatment response. High brain uptake, relatively high skin background and the smaller diameter of the vessels lower the sensitivity of F-18 FDG PET in temporal arteritis. Giant cell arteritis in arteries greater than 4mm in diameter is nicely demonstrated by F-18 FDG PET. It is important to remember that vasculitis can be one of the causes of FUO as we have observed in some of our referred patients (Figure 11). Assessment for this is done by observing both non-attenuation corrected and attenuation corrected PET images.

Fig. 11. A 56-year old female with FUO referred for detecting potential site(s) of infection. F-18 FDG PET/CT scan show diffuse increased FDG uptake evident in major blood vessels including the carotids, brachiocephalics, aortic arch, descending thoracic aorta extending up to the renal level. Findings consistent with the inflammatory etiology of vasculitis.

In patients with HIV-AIDS, there is increased likelihood of opportunistic infections as well as malignancy. (O'Doherty et al., 1997) reported that F-18 FDG PET has a sensitivity of 92% and specificity of 94% in localizing abnormalities that required treatment in these patients; however, they also concluded that it is not possible to clearly distinguish infectious from a malignant process in these patients. Toxoplasmosis is the commonest of the opportunistic

vessel walls cannot be detected in the early phase on conventional anatomical imaging. F-18 FDG assists in early diagnosis, assessing the extent of the disease and has also been found superior to MRI in depicting disease activity and treatment response. High brain uptake, relatively high skin background and the smaller diameter of the vessels lower the sensitivity of F-18 FDG PET in temporal arteritis. Giant cell arteritis in arteries greater than 4mm in diameter is nicely demonstrated by F-18 FDG PET. It is important to remember that vasculitis can be one of the causes of FUO as we have observed in some of our referred patients (Figure 11). Assessment for this is done by observing both non-attenuation

Fig. 11. A 56-year old female with FUO referred for detecting potential site(s) of infection. F-18 FDG PET/CT scan show diffuse increased FDG uptake evident in major blood vessels including the carotids, brachiocephalics, aortic arch, descending thoracic aorta extending up

In patients with HIV-AIDS, there is increased likelihood of opportunistic infections as well as malignancy. (O'Doherty et al., 1997) reported that F-18 FDG PET has a sensitivity of 92% and specificity of 94% in localizing abnormalities that required treatment in these patients; however, they also concluded that it is not possible to clearly distinguish infectious from a malignant process in these patients. Toxoplasmosis is the commonest of the opportunistic

to the renal level. Findings consistent with the inflammatory etiology of vasculitis.

corrected and attenuation corrected PET images.

infections in AIDS patients. Most commonly the central nervous system is affected. F-18 FDG has been reported to be superior and more accurate than MRI in differentiating CNS lymphoma from conditions such as toxoplasmosis, progressive multi-focal leukoencephalopathy and syphilis. Further on quantitative assessment it has been shown that the standardized uptake values of toxoplasmosis are significantly lower than lymphoma with virtually no overlap.

F-18 FDG PET has been used extensively to evaluate painful lower limb joint prostheses. It has a limited significance especially when distinguishing infected joint prosthesis from aseptic prosthetic loosening. As inflammation is part of both the conditions, there is increased F-18 FDG peri-prosthetic accumulation observed in both. F-18 FDG PET is considered highly sensitive for evaluation of chronic osteomyelitis. Unlike bone scintigraphy F-18 FDG uptake normalizes in less than 2-3 months following treatment, thereby, reducing the false positive scans seen when osteomyelitis is suspected in complicated fractures. F-18 FDG PET has also been used with variable utility in diabetic foot infections, sarcoidosis, tuberculosis, organ transplantation and inflammatory bowel disease. In case of sarcoidosis the imaging findings are similar to those seen and discussed with Ga-67 scintigraphy. Further F-18 FDG PET can detect metastatic infectious foci with high sensitivity even if other imaging is negative.
