The Role of Nuclear Medicine in

Infection/inflammation

The Role of Nuclear Medicine in

Infection/inflammation

A.A.Hussein S. KartamihardjaHussein S. KartamihardjaDepartment of Nuclear Medicine and

Molecular ImagingFaculty of Medicine Universitas

PadjadjaranDr. Hasan Sadikin General Hospital

• a major cause of mortality and morbidity not only in the developing countries, but globally.

• Multi drug resistant and tuberculosis are increasing and provide diagnostic, therapeutic and infection control challenges.

• In most of case the diagnosis of infection is very clear based on history, physical examination and identification of microorganisms in pus, blood, or body secretion.

• But in many cases imaging modalities are needed to detect and locate the site of infection.

Infection

Department of Nuclear Medicine and Molecular ImagingPadjadjaran University – Dr. Hasan Sadikin Hospital

Imaging techniques for diagnosis and localization of infection and inflammation

• Based on anatomical changes

1. Conventional x-ray

2. CT scan

3. MRI

4. USG

• Based on physiological changes

• Nuclear medicine

Nuclear medicine techniques are often used in the context of fever of unknown origin or suspected bacterial infection to aid diagnosis and to establish the need for antimicrobial treatment.

Nuclear medicine in infection and inflammation

• Detection of infection / inflammation is a challenging problem in clinical practice, because it may have important implications for the management of patients with infectious or inflammatory diseases.

• NM played an important role in the diagnosis and localization of infection and inflammation since the use of Gallium-67 citrate in 1970’s

Department of Nuclear Medicine and Molecular ImagingPadjadjaran University – Dr. Hasan Sadikin Hospital

Radiopharmaceutical for infection and inflammation

Non specific Specific process Specific diseaseGa-67 citrate In-111 oxine-wbc Tc-99m cyprofloxacine

Tc-99m albumin Tc-99m HMPAO-wbc Monoclonal antibody

Tc-99m Nano colloid

Peptide labeled Tc-99m UBI

F-18 FDG Polyclonal-antibody (Tc-99m-HIg)

Tc-99m Ethambutol

The radiopharmaceutical used for imaging infection The radiopharmaceutical used for imaging infection and inflammation accumulates in the and inflammation accumulates in the infectious/inflammatory lesion due to the locally infectious/inflammatory lesion due to the locally changed physiological condition. changed physiological condition.

Characterized by :Characterized by :• enhanced blood flowenhanced blood flow• enhanced vascular enhanced vascular permeability permeability • influx of white blood cellsinflux of white blood cells

Department of Nuclear Medicine and Molecular ImagingPadjadjaran University – Dr. Hasan Sadikin Hospital

1. efficient accumulation and good retention in inflammatory foci

2. rapid clearance from background 3. no accumulation in non-inflamed tissues 4. no side-effects 5. low cost (Tc-99m) and easy preparation (kit

formulation) 6. discrimination between infection and non-

microbial inflammation

The ideal The ideal radiopharmaceutiradiopharmaceutical for cal for infection/inflamminfection/inflammation imagingation imaging

Bone imaging• Ability to image osteoblastic activity.

• Widely available, accurate and cost-effective examination

• The increased Tc-99m MDP uptake is a good indicator of infection or loosening with 100% sensitivity and 72% specificity. (Weiss et al 1979)

• Recommended as an initial study. Negative results could be treated conservatively.

• To improve the accuracy in hip prosthesis, the baseline scan should be done 9-12 months after surgery and at a time when the patients develop symptoms

• Three-phase bone imaging. • Combines dynamic and static

bone imaging• Arterial, soft-tissue and bone-

metabolic phase

White blood cell labeling

• Leukocytes are the major component on inflammatory and immune responses

• Normally about 90% of neutrophil pool is in the bone marrow, only 2-3% is in the circulation

• In an acute inflammatory, neutrophils migrate toward an attractant (chemotaxis), increase their adhesiveness, aggregate, adhere to endothelial surface, phagocytize the infectious agents or foreign bodies and enzymatically destroy it within cytoplasmic body.

• Neutrophils survive in tissue only 2-3 days

• In-111 oxine or Tc-99m HMPAO

• In-111 is cyclotron produced radionuclide

• Half life 67 hrs

• Gamma photon 173 keV and 247 keV

• In-111 oxine label blood cell indiscriminately

• Labeling wbc with I-111 oxine will take about 2 hours

• Careful handling is necessary to avoid damaging the cell and other contaminations

• Labeling efficiencies of more than 75% is sufficient

• Increased lung uptake can be used as a parameter of poor labeling quality due to cell damage 89-year-old male with FUO

In-111-labeled In-111-labeled white blood cellwhite blood cell

In-111-labeled In-111-labeled white blood cellwhite blood cell

• Hexamethylpropyleneamineoxine, is a lipophilic and readily crosses the white cell membrane

• Intracellularly, it changes into a hydrophilic complex and becomes trapped, bound to mitochondria and the nucleus

• Widely use for diagnosing and localizing infection and inflammation

• Preparation and procedure of imaging is similar to In-111 oxine, except photopeak at 140 keV.

Tc-99 m HMPAO WBC

Both the 90 min peptide and 24 h in vitro-labeled leukocyte images demonstrate focal, intense uptake in the distal third of the left tibia of a 45-year-old man with osteomyelitis of this bone.

• There are many radiopharmaceutical have been used for diagnosing and localizing of infection and inflammation, but to differentiate bacterial infection from sterile inflammation is still a problem until 1995 when Infecton was discovered.

• Infecton, basically is cyprofloxacine, a broad spectrum antibiotic

• Invitro studies showed, that infecton can be trapped by living pathogen bacteria and destroy DNA gyrase, but not non-pathogen bacteria

• Infecton still can be trapped in bacterias resistant to cyprofloxacine

• There are many radiopharmaceutical have been used for diagnosing and localizing of infection and inflammation, but to differentiate bacterial infection from sterile inflammation is still a problem until 1995 when Infecton was discovered.

• Infecton, basically is cyprofloxacine, a broad spectrum antibiotic

• Invitro studies showed, that infecton can be trapped by living pathogen bacteria and destroy DNA gyrase, but not non-pathogen bacteria

• Infecton still can be trapped in bacterias resistant to cyprofloxacine

Tc-99m ciprofloxacinTc-99m ciprofloxacinTc-99m ciprofloxacinTc-99m ciprofloxacin

Department of Nuclear MedicinePadjadjaran University – Dr. Hasan Sadikin Hospital

Tc-99m HMPAO-Tc-99m HMPAO-WBCWBC

Tc-99m InfectonTc-99m Infecton

Sensitivity 93%

Specificity 71%

Positive predictive value 88%

Negative predictive value 83%

The Use of 99mTc-Ciprofloxacin (Infecton) Scintigraphy in Detection of Cervical Lymphadenitis.Aisyah Elliyanti*, Kurniadi**, A.Hussein S Kartamihardja*, and Johan S Masjhur*

*Department of Nuclear Medicine **Department of Surgery Dr. Hasan Sadikin Hospital Bandung-Indonesia

23 subjects with cervical lymphadenopathy; histopathologic examination by open biopsy23 subjects with cervical lymphadenopathy; histopathologic examination by open biopsy

Results :• Positive scan : 16 1 / 16: tumor metastases.

• Negative scan : 7 2 / 7: tuberculous infection treated by tuberculoustatic for one year and amoxicillin

Tc-99m Ciprofloxacin

Spondylitis Tuberculosis

• Specific antituberculous

• Micoic acid in baterial wall

• Tc-99m labelled

Three serious foot complications of Three serious foot complications of diabetes mellitusdiabetes mellitus

Foot ulcerations,

infections, and

Charcot neuropathic osteoarthropathy

• It is needed to determine

• which of treatments are most effective.

• How to effectively prevent those ulcerations which are leading to amputation

• The detection of diabetic foot infection can be difficult. With clinical examination, it is difficult to differentiate between soft-tissue infection and osteomyelitis.

• The erythrocyte sedimentation rate is not specific.

• Bone biopsy is not always performed because it is an invasive procedure that loses its reliability when the biopsy fragment is contaminated by cutaneous bacteria.

• Imaging modalities are valuable for the diagnosis and crucial in the evaluation of infections in DM.

Hell J Nucl Med 2010; 13(2):150-157

• SPECT/CT can represent a potential tool for diagnosing diabetic foot infection by 99mTc-HMPAO–labeled leukocytes by differentiating between bone and soft-tissue involvement and by more precisely defining the extent of the disease, thus supporting treatment planning and avoiding more invasive procedures

• TPBS is a useful clinical tool to assist the orthopedist in making a more objective decision regarding the amputation level of ischemic lower limbs and surgical procedure to be employed, prior to surgery