Continues Assessment: Written Assignment
Title: PET/CT Infection and Inflammation
STUDENT N.O: 215122534
FACULTY:Health and Wellness Sciences
DEPARTMENT:Medical Imaging and Therapeutic Sciences
QUALIFICATION: BSc: Nuclear Medicine Technology
SUBJECTS: Advanced Nuclear Medicine Technology 4
DUE DATE:October 2018
EXAMINERS: C Lackay,
Moderator: T Eiselen
Table of Contents
TOC o “1-3” h z u PLAGIARISM DECLARATION PAGEREF _Toc526811285 h iii1.Introduction PAGEREF _Toc526811286 h 12.Imaging of Infectious Disease/ inflammation PAGEREF _Toc526811287 h 1i.WBC scintigraphy PAGEREF _Toc526811288 h 3ii.18F-FDG-PET/CT PAGEREF _Toc526811289 h 43.Significance of PET/CT in imaging infection/ inflammatory. PAGEREF _Toc526811290 h 41.Osteomyelitis PAGEREF _Toc526811291 h 52.Infected prosthesis PAGEREF _Toc526811292 h 63.Diabetic foot PAGEREF _Toc526811293 h 84.Soft tissue infection PAGEREF _Toc526811294 h 95.Pitfalls of PET/CT PAGEREF _Toc526811295 h 116.Future Trends PAGEREF _Toc526811296 h 137.Conclusion PAGEREF _Toc526811297 h 138.Appendixes PAGEREF _Toc526811298 h 13References PAGEREF _Toc526811299 h 13
Faculty of Health and Wellness Sciences
Medical Imaging and Therapeutic Sciences
PLAGIARISM DECLARATIONThis declaration must accompany every assignment / case study and must be bound into the submission after the cover page.
I Akhona Ndlela …Declare that the following assignment is my own original work, compiled without assistance, or involvement of fellow students. All sources used, or quoted, have been indicated and acknowledged by means of using the Harvard system of in-text and end-of text referencing, i.e. I have NOT PRACTISED ANY FORM OF PLAGIARISM.
COURSE: BSc Nuclear Medicine Technology.
SUBJECT: Advanced Nuclear Medicine Technology 4
TITLE: PET/CT Infection and Inflammation
Signed this Day of October 2018
Student Full Name & Surname: Akhona Ndlela
Student Number: 215122534
Recipient Signature: _______________________________________________
Infection is the colonisation of body tissues by microorganisms such a bacteria, virus, or fungi. Infection cases inflammation. Therefore, inflammation is the bodies general response to disease that occur secondary to infection tumour or physical trauma or conditions both located and wide spread1. The clinical indications for inflammatory for nuclear medicine include; Fever of unknown origin, retroperitoneal fibrosis, suspected osteomyelitis or diskitis, pulmonary and mediastinal inflammation/infection, lymphocytic or granulomatous inflammatory processes (sarcoidosis/ tuberculosis), Drug-induced pulmonary toxicity or acute or chronic inflammation/ infection (Christian) .
When a patient is suspected to have infection of inflammation the general practitioner will try to make prompt and accurate diagnosis 2. Accurate diagnoses are important form initiating appropriate therapy and patient’s management2. In most times disease are easily detected by the use of exposing patient’s specimens to a microscope3. When diagnosis is challenging in terms of localising the area affected imaging modalities are employed to assist with farther investigation or diagnosis3.
Metabolic and functional imaging techniques may be useful in these investigations. Nuclear medicine procedures have been developed recently to assist in these diagnostic investigations. In these instances the investigator may use various techniques and radionuclides such as 51Cromium, 32Phosphorus- disoflourophosphate, 67Gallium citrate, 99mTechnetium (99mTc)-labelled white blood cells, 111Indium-labelled white blood cells and 18Flourine-Flourodeoxi-glucose4. Some of these radioisotope and radiopharmaceuticals are used for labelling blood such as white blood cell labelling and to study the cell survival4. Some radioisotopes are proposed by researchers to be used in the future, to assist with diagnosing and localising infections and inflammations.
Imaging of Infectious Disease/ inflammation
Early diagnosis or exclusion of infection and inflammation is of utmost importance for the optimal management of patients with such common disorders5. However in certain settings these diagnoses can be made without difficulty in most other situations the clinicians encounter challenges in detecting and localizing the exact site of infection. These difficulties are commonly encountered in the management of disorders such as pulmonary, intra-abdominal and cerebral processes. However in pyrexia of unknown origin, spinal infection and complicated osteomyelitis the challenges are greater2. Even greater challenges are encountered in view of the increased use of immune suppressive agents, in patients who underwent transplants, in patients who have received anti-cancer therapies and patients with acquired immunodeficiency syndromes (AIDS). Clinicians often refer their patients for farther diagnostic procedures and modalities2.
Morden imaging techniques such as computed tomography (CT) and Magnetic Resonance Imaging (MRI) can be used to achieve certain diagnostic procedures2. The cross sectional imaging techniques have provided to have excellent structural resolution of the infected and inflamed organ or body part5. This is because of their spatial resolution that these modalities have allowed clinicians to accurately have depth information of a superficial infection and aiding in diagnosis and surgical planning2. However these modalities are generally of limited value in detecting early disease regardless of the cause. Therefore, functional and metabolic imaging techniques are often needed to complement the role of anatomic imaging modalities in most clinical setting5.
In the advent of 67Ga-citrate for routine infection imaging a variety of agents have been developed and evaluated to better localize and detect areas of infection within the body of a human6. There has been some great development since the introduction of the radiopharmaceutical, but a true infection specific imaging agent has yet to be developed. Almost all of the commonly used imaging agents localize to areas of inflammation rather that specifically those of infection. This however results in difficulties in clinical interpretation and at times it is unreliable to use them as planning for aggressive therapeutic intervention6. As described early inflammation and infections are different processes. It is important for clinicians to recognize that all radiopharmaceuticals accumulate to some extent as the results of inflammation at the site of infection6.
WBC scintigraphyAn advancement over the original 67Ga-citrate infection imaging was the development of in-vivo radiolabelling white blood cells (WBC labelling) using 111In-oxine4 or 99mTc-Hexamethyli-propylene amine axime (99mTc-HMPAO). The chemotaxitic properties of the activated leukocytes form the basis of labeled leukocyte imaging. The various problems encountered in leukocyte labelling will be discussed. However one disadvantage worth mentioning is the in ability to differentiate infection related to urinary and gastrointestinal system6.
According to Perizzi, et al, continues research in this field led to the development of labelled antibiotics. 99mTc- labeled ciproflocacine was reported to bind to the deoxyribonucleic acid (DNA) gyrase of living bacteria, thereby distinguishing bacterial infection from inflammation. There are several other agents that have been found to have an effect in infection imaging. Ubiguicidin analogs is one of the examples, this chemotactic peptide fragment and other non-peptide molecules such as leukotriene antagonists can bind to the leukocytes and provide imaging of the infected area6.
Most of the major challenges faced when performing WBC imaging is the cell labelling procedure. Other problems arise from the misreading the scan because of the incorrect acquisition protocol or interpretation criteria or both7. WBC should be labelled with the above mentioned radiopharmaceuticals, this is according to the published guidelines of the inflammation and infection task group of the European Association of Nuclear Medicine7, 8. These guidelines are written in accordance with the International Atomic Energy Agency (IAEA) recommendations. Disregarding this regulation can result in pitfalls such as lack of uptake in an infectious process or the presence of false- positive uptake in non-infected sites such as the lungs7.
Whether WBC should be performed on patients receiving antibiotics therapy is still a debate. It is known that certain antibiotics lower the total number of WBC7. However various studies have found no significant deference in the diagnostic accuracy of WBC scintigraphy between patients on and off antibiotics therapy at the time of the study.
18F-FDG-PET/CTA new technique that has recently gained favour in clinical use is that of positron emission tomography/ computed tomography (PET/CT) imaging for the rapid detection and localization of occult infection6. 18F-FDG has been shown to target site s of infection via increased glucose utilization by infiltrated granulocytes and macrophages due to metabolic requirements. However this is also non-specific because 18F-FDG is also taken up at nonspecific sites of inflammation as well as sites or malignance. The sensitivity of 18F-FDG-PET/CT in patients suspected with focal infection is reported to be similar to that of 111In-labelled leukocytes. However false positive changes are seen in patients with malignancy, in the postoperative period, and other post therapy (radiation therapy), which leads to low specificity of 18F-FDG-PET/CT6.
18F-FDG is a positron emitter with a half-life of 110 minutes. 18F-FDG is transported through the cellular membrane by glucose transporter proteins and is subsequently phosphorylated to 18F-FDG 6 phosphates by hexokinase enzyme. Only few studies have tried to clarify the mechanism of 18F-FDG uptake in inflammatory cells in-vitro. In these studies either mixed preparation of WBC or pure preparations of granulocyte and mononuclear cells used. However due to poor labelling stability, in-vitro 18F-FDG labelled cells are not suitable for clinical application.
Significance of PET/CT in imaging infection/ inflammatory.
18F-FDG-PET have many advantages over other nuclear medicine imaging procedures and modalities used for diagnosis of infectious and inflammatory disease5. 18F-FDG combine with many advantages when associated with CT alone. The Optimal spatial resolution, precision and lack of metallic artefacts is the key in optimal diagnosis and accurate imaging method. 18F-FDG-PET has shown superiority over imaging with radiolabelled WBC with an accuracy exceeding 90% in the clinical setting.
The high diagnostic accuracy of PET imaging compared with 67Ga-citrate scintigraphy may be explained by the preferable tracer kinetic of the small 18F-FDG molecules compared with the relatively large 67Ga-citrate transferrin complex and by the better spatial resolution of coincidence imaging in comparison with a conventional gamma camera5 Data of the clinical indication for 18F-FDG-PET imaging of infection and inflammation are still limited but nevertheless very promising. A wide rand of infectious conditions such as osteomyelitis, infected prosthesis, diabetic foot, soft tissue infections such as acute and chronic pancreatitis, sarcoidosis, tuberculosis occult infection, auto-immune fibrosis, inflammation in post-operative fever, fever of unknown origin and inflammation in HIV positive patients have been successfully visualised 18F-FDG-PET in limited series.
OsteomyelitisThe data on the role of 18F-FDG-PET on diagnosing osteomyelitis is increasingly promising. Osteomyelitis is a bone infection and is usually caused by bacterial, fungal or mycobacterial micro-organisms. The accurate diagnosis of subacute or chronic osteomyelitis is often difficult by physical examination and existing radiological or nuclear medicine techniques, in particular when there are pre-existing bone alterations. The use of radiolabelled WBC imaging combined with bone marrow scintigraphy has reported been reported to be highly accurate in detecting chronic osteomyelitis. Though the significance of radiolabelled WBC is affected if the patient has been treated with antibiotics prior to imaging.
However, 18F-FDG-PET has shown to be highly sensitive for detecting chronic osteomyelitis even in patients who have been treated with antibiotics. 18F-FDG-PET appear to hold great promises as being the choice of study for diagnostic imaging of chronic osteomyelitis. It has been proven to be successful in detecting the disease in different type skeletal system. It is also significant in any bone where there is increased concentration of red bone marrow. This overthrows bone scintigraphy as it remains positive for an extended period8, 9.
0-4445Fig1: “Fluorodeoxyglucose positron emission tomography (FDG PET). (A), Serial scans showing evidence of osteomyelitis in June 2016. (B), Partial resolution in October 2016; (C). Near complete resolution in April, 2017” Gupta et al., 2017:2.
0Fig1: “Fluorodeoxyglucose positron emission tomography (FDG PET). (A), Serial scans showing evidence of osteomyelitis in June 2016. (B), Partial resolution in October 2016; (C). Near complete resolution in April, 2017” Gupta et al., 2017:2.
01457960Fig 2: “PET/CT obtained several year after motorcycle accident with recurrent and increasing pain in the left lower leg and soft tissue tenderness over the tibia (A-D). PET demonstrate increased uptake in the tissue as well as in the bone marrow cavity of the tibia, suggesting the diagnosis of osteomyelitis, which was confirmed surgically” Stumpe et al., 2016:
00Fig 2: “PET/CT obtained several year after motorcycle accident with recurrent and increasing pain in the left lower leg and soft tissue tenderness over the tibia (A-D). PET demonstrate increased uptake in the tissue as well as in the bone marrow cavity of the tibia, suggesting the diagnosis of osteomyelitis, which was confirmed surgically” Stumpe et al., 2016:
Infected prosthesisA large number of patients with degenerative diseases of the hip or knee joint get prosthesis implants. 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 underwent. Radiolabelled WBC is the, bone scintigraphy is the first step a clinician take is diagnosing the patient. However, their sensitivity is outweighed by that of 18F-FDG-PET imaging. 18F-FDG-PET has greater potential for examinations of patients with suspected hip and knee prosthetic infection.
18F-FDG has shown to localise around the prosthesis and the infected area. In contrast in patients with loosening of the hip prosthesis, but without infection intense uptake around the femoral head or neck components of the prosthesis can also be observed (referee to figure 3 D-E and figure 4). However, the amount of activity around the area is less important than the actual localisation in the affected area. The diagnostic performance of 18F-FDG-PET scan in detecting painful hip and knee prosthesis is optimal for routine clinical application. Lastly 18F-FDG-PET scan appears to be an appropriate alternative for assessing the conditions9.
According to Dumarey (2009) and Aksoy et al (2014), the avidity of inflammatory cell FDG has led to the concept of labelling leukocytes with 18F-FDG ex-vivo. This concept combines cell bound radionuclide trafficking from blood pool compartment to the lesion with the high resolution with the high resolution of PET imaging. The feasibility and potential value of leukocyte PET/CT imaging in infection have been demonstrated in figure 4.
04445Fig 3: “Typical FDG-PET findings in a patient with infection of the hip prosthesis (bilaterally), which was subsequently proven. Significant uptake of FDG seen in the bone-prosthesis interface is characteristic of this complication” Kumar et al., 2008:214 .
Fig 3: “Typical FDG-PET findings in a patient with infection of the hip prosthesis (bilaterally), which was subsequently proven. Significant uptake of FDG seen in the bone-prosthesis interface is characteristic of this complication” Kumar et al., 2008:214 .
476253439160Fig 4: “A 47-year-old female patient who had undergone right knee arthroplasty presented with right knee pain. Selected coronal PET/CT images (a, b) and maximum intensity projection PET/CT images (c) are shown. The FDG PET/CT images (two left columns) show intense activity (grade 3b) around the right knee prosthesis. FDG- labelled leucocyte PET/CT images (two right columns) show no significant uptake around the prosthesis. The final microbiological diagnosis confirmed aseptic loosening of the right knee prosthesis” Aksoy et al., 2014:562.
0Fig 4: “A 47-year-old female patient who had undergone right knee arthroplasty presented with right knee pain. Selected coronal PET/CT images (a, b) and maximum intensity projection PET/CT images (c) are shown. The FDG PET/CT images (two left columns) show intense activity (grade 3b) around the right knee prosthesis. FDG- labelled leucocyte PET/CT images (two right columns) show no significant uptake around the prosthesis. The final microbiological diagnosis confirmed aseptic loosening of the right knee prosthesis” Aksoy et al., 2014:562.
Peripheral neuropathy is common in patients with diabetes mellitus and can result in foot ulceration and ultimately, the destruction of osseous structure due to Charcot osteorthropathy and osteomyelitis. Osteomyelitis comprises of 33% of the diabetic foot infection and is often due to direct, contiguous contamination from the soft tissues lesions. It is however important to recognise these effects clinical because early diagnosis and treatment with antibiotics are essential to prevent amputation. When 18F-FDG-Pet is used, it well known that many diabetic mellitus patients become hyglyci,iwc after the administration of the radiopharmaceutical (18F-FDG). It also known that hyperglycemia adversely affect the uptake of 18F-FDG in many type of malignant lesion and thefefore lowers the sensitivity of the of the scan.
However, the accuracy of 18F-FDG-PET for pedal osteomyelitis detection in diabetic patients seems minimal. In general, that quality of 18F-FDG-PET images for assessing infection is optimal when serum glucose level are less that 250 mg/dL. 18F-FDG-PET is belived to be the next is the next golden technique that should be used to evaluate and study the complicated diabetic foot in the clinical practices.
571501620520Fig 5: “PET/CT images in a 61-year-old man with an abscess in the right foot. Maximal intensity projection and transaxial PET images show an area of increased FDG uptake (SUVmax 10) in the medial aspect of the right forefoot (a, b). In the PET/CT image this uptake is localized solely to soft-tissue swelling surrounding the first metatarsal” Kagna et al., 2012:1549.
00Fig 5: “PET/CT images in a 61-year-old man with an abscess in the right foot. Maximal intensity projection and transaxial PET images show an area of increased FDG uptake (SUVmax 10) in the medial aspect of the right forefoot (a, b). In the PET/CT image this uptake is localized solely to soft-tissue swelling surrounding the first metatarsal” Kagna et al., 2012:1549.
Soft tissue infectionAs discussed above 18F-FDG-PET has the ability to images different infection from soft tissue namely: TB, FUO, pericarditis, and vasculitis. When it comes to fever of unknown origin, it is defined as fever of higher than 38oc that has been documented on several occasions with duration of at least 3 weeks and an urecertian source after 1 week of comprehensive investigation with conventional techniques as an inpatient in the clinical setting. 18F-FDG-PET allows the identification of inflammatory and cancerous disorders as the underlying cause of FUO in most patients and has shown to detect infectionious and inflammatory disease process that were undetected when conventional scintigraphy techniques or MRI was used10 (see figure 8).
TB remains a threat to human with high mortality rising incidence of multidrug resistance and HIV co-infection (Ankrah et al., 2016). Despite the availability of relatively cheap and effective treatment options TB has remained the second leading cause of death worldwide. The sputum test has been effectively used to diagnoses TB for over 130 years. However, sputum test is difficult to obtain from infants and children. Plan X-ray /CT are the centrepiece for diagnostic imaging for pulmonary TB, But are often no–specific and unable to provide a definitive diagnostic due to the heterogeneous presentation, particularly in case of HIV co-infection when CD4 counts are very low.
PET/CT has the ability to associate the pharmacological immunologic and microbiological aspect of TB lesion with anatomical information allowing a holistic approach to understanding the disease. The value of imaging TB with 18F-FDG-PET/CT has been demonstrated in figure 6&7. 18F-FDG-PET/CT has been used to detect TB granulomas and assess disease activity and the extant of disease. Active TB avidly takes up 18F-FDG, both in pulmonary and extra-pulmonary lesions. Therefore, 18F-FDG-PET/CT can be very useful to assess the extent of active TB (Ankrah et al., 2016)
-6667516510Fig 6: “(A-D): Disseminated TB with multifocal hepatic and diffuse splenic uptake. Coronal plain CT (A) and PET (B) with axial PET/CT (C, D) images in a patient with FUO show diffuse increased FDG uptake in an enlarged spleen and multifocal uptake in the liver, mediastinal nodes, and patchy lung lesions (arrows). Transbronchial sampling from the subcarinal nodes revealed tuberculosis. PET in this case guided the tissue sampling from an active lesion in an accessible site, using the least invasive route” Hrkirat et al., 2008:43.
Fig 6: “(A-D): Disseminated TB with multifocal hepatic and diffuse splenic uptake. Coronal plain CT (A) and PET (B) with axial PET/CT (C, D) images in a patient with FUO show diffuse increased FDG uptake in an enlarged spleen and multifocal uptake in the liver, mediastinal nodes, and patchy lung lesions (arrows). Transbronchial sampling from the subcarinal nodes revealed tuberculosis. PET in this case guided the tissue sampling from an active lesion in an accessible site, using the least invasive route” Hrkirat et al., 2008:43.
368744596520Fig 7: “(A-D): Pulmonary tuberculosis. A sputum positive case of pulmonary TB with clinically poor response to 2 months of antituberculous therapy. Coronal plain CT (A) and PET/CT (B) with axial plain CT (C) and PET/CT (D) images reveal extensive FDG-avid pulmonary parenchymal lesions. The superior segment of the left lower lobe shows consolidation with central cavitation (arrows) with an SUV max of 10.1. These fi ndings suggest active disease, indicating an inadequate response to therapy” Hrkirat et al., 2008:45.
Fig 7: “(A-D): Pulmonary tuberculosis. A sputum positive case of pulmonary TB with clinically poor response to 2 months of antituberculous therapy. Coronal plain CT (A) and PET/CT (B) with axial plain CT (C) and PET/CT (D) images reveal extensive FDG-avid pulmonary parenchymal lesions. The superior segment of the left lower lobe shows consolidation with central cavitation (arrows) with an SUV max of 10.1. These fi ndings suggest active disease, indicating an inadequate response to therapy” Hrkirat et al., 2008:45.
-472975986839Fig 8: “18F-FDG PET (from left to right: coronal, sagittal, and transversal slices) of 65-y-old patient with long-standing FUO 6 years after revision of aortic aneurism, which was replaced by vascular graft. PET scan demonstrates elevated uptake in graft extending to adjacent tissue. Infection of graft was subsequently proven during diagnostic work-up” Meller et al., 2007:38.
Fig 8: “18F-FDG PET (from left to right: coronal, sagittal, and transversal slices) of 65-y-old patient with long-standing FUO 6 years after revision of aortic aneurism, which was replaced by vascular graft. PET scan demonstrates elevated uptake in graft extending to adjacent tissue. Infection of graft was subsequently proven during diagnostic work-up” Meller et al., 2007:38.
Pitfalls of PET/CT The major limitations of 18F-FDG-PET/CT is the inability of the tracer to discriminate between malignance, infection and inflammation7. Accumulation of leukocytes, macrophages, monocytes, lymphocytes and giant cell constitutes the body’s response to injury and infection. Upredulation of glucose transportors has been demonstrated in all these cell lines and contributes to the uptake of detectable amounts of 18F-FDG in infection and inflammation, as well as in regenerating and traumatic processes7. Clinicians should be aware of these limitations: for example to avaiod potential pitfals in skeletal 18F-FDG uptake. A careful evaluation of the combination of CT component is necessary to exclude factors such as recent fracturs as a cause of increased increased 18F-FDG uptake.
It is still controversial whther hyperglycemia or diabetes mellitus affects the sensitivity of 18F-FDG-PET/CT imaing. Guidelines for 18F-FDG-PET/CT in patients with cancer recommend that 18F-FDG should not be administered when blood glucose level exceeds 200 mg/dL or even 120 mg/dL if clinically possible. Kidney function may also have an influence on the scan quality. The target to background raio will decrease owing to a high and longer uptake in cardiovascular structure ( high blood pool activity). Therfore serum creatinine level or glomerular filtration rate or both should be checked before performing the study- kidney function is already routinely checked clinically or before CT imaging with contrast.
Some other pitfalls include invasive procedures which often results in 18F-FDG increased uptake due to regeneration and healing process of the area. In children and young adults physiological uptake of the 18F-FDG in the thymus can be expected more often after chemotherapy. A diffused homogeneous 18F-FDG uptake in bone marrow can also be visualised any many conditions,, the relate to a pathology process, such as diffused bone marrow metastases leukaemia or myelodysplastic syndromes. The most popular potential pitfall for 18F-FDG-PET/CT imaging include the uptake in brown fat activity and physiological uptake in ovaries, endometrium and breast tissue. However these conditions are not regarded as pitfalls for imaging infectious and inflammatory disorders.
Some of the Pitfalls may arise due to medication and treatment procedures that a patient is undergoing or has undergone. These medications includes steroids treatment which may result in false negative scan finding and should be stopped or avoided if a patient is top undergo a 18F-FDG-PET/CT scan. Antibiotics are also suspected to have an influence in 18F-FDG uptake (lower 18F-FDG uptake) in infectious processes, however there no studies confirming this assumption. A drug that is known to have influence on 18F-FDG uptake is metformin. This is an antihyperglycemic drug used by patients with type2 diabetes mellitus. Administration of metformin is associated with intense and diffuse 18F-FDG uptake in small infectious or inflammatory lesions leading to false-negative results. Another drug that has shown to have an influence on 18F-FDG uptake is ipilimumb. This is a monoclonal antibody used to activate the immune system and is mostly used by patients with melanoma. This drug results in increased 18F-FDG bowl uptake
There is and inclining need for procedures that are non-invasive and can be performed reputedly without putting patients in to any potential harzards2. These procedures should obviate the need for invasive procedures such as biopsy. These procedures should be used for assessing the effectiveness of therapy.
The recent developments in the field have substantially improved the abilities of nuclear medicine techniques to detect infectious disease and inflammation2. These modalities include the use of single photon emission computed tomography (SPECT) with the use of tracers such as radiolabelled chemocitic peptide, radiolabelled liposome, avid-mediated imaging, radiolabelled antibiotics (such as ciproflourine) and monoclonal antibodies. Some of these agents could also be labelled with positron emitters such as 18F and 68Ga and can be applied for PET imaging2.
Aksoy, S.Y., Asa, S., Ozham, M. ; Ocak, . 2014. Europian Journal of Nuclear Medicine and Molecular Imaging. FDG and FDG lebaellied luecocyte PET/CT in the imaging of prosthetic joint infection, 41:556-564. October.
Gupta, N. Banerjee, S. ; Shama, R. 2017. Research gate. Osteomyelitis due to multiple rare infections in patients with idiopathic CD4 lymphocytompaenia. July. DOI:10.5582/irdr.2017.01029. 09-Oct-2018.
Harkirat, S., Ananna, S.S., Indarjit, L.K. ; Dash, A.K. 2008. Indian Journal of Radiology and imaging. Pictorial essay: PET/CT in tuberculosis, 18(2): 141-147. May.
Kagna, O., Srour, S.F. ; Keidar, Z. 2010. Europian Journal of Nuclear Medicine and Molecular Imaging. FDG-PET/CT imaging in the diagnosis of osteomyelitis in the diabetic foot, 39(10): 1545-1550. April.
Kumar, R., Basu, S., Torgian, D. ; Alavi, A. 2008. Clinicak Microbiology. The Morden imaging techniques for diagnosis of infection in the era of 18F-Fluorodeoxyglucose- Positron Emiossion Tomography. 21(1):209-224. February.
Meller, J., Shalmann, C.O. ; Scheel. A.K. 2007. Journal of Nuclear Medicine. 18F-FDG-PET and PET/CT in Fever of unknown origin, 48:35-45. January.
Stumpe, K.D.M., Strobel, K. ; Hodler, J. 2016. Radiology Key. Masculoskeletal infections: PET-CT and SPECT/CT imaging. July. https://radiologykey.com/musculoskeletal-infections-pet-ct-and-spect-ct-imaging/. 09 Oct 2018.