Radionuclide Imaging of Infection/inflamation MUDr.Kateřina Táboská

Based on physiochemical processes in tissues Accumulation in the lesion due to the locally changed physiological condition: increased blood flow enhanced vascular permeability influx of white blood cells

AGENTS Labeled Leukocytes 67Gallium –citrate 18FDG 99mTc MDP

Labeled Leukocytes Uptake of labeled leukocytes is dependent on Intact chemotaxis The number and types of cells labeled total white count – 2x109/l , neutrophils 3) The cellular component of a particular inflammatory response : neutrophil – mediated inflammatory processes - bacterial infections

Labeled leukocytes In vitro: 111In – oxine 99mTc- HMPAO (hexamethylpropyleneamine oxime) 60ml of whole blood is withdrawn Separation the WBC Incubation with the radiolabel Reinjection into the patient

Labeled leukocytes 2) In vivo: 99mTc murine monoclonal antibody against leukocyte cell membrane antigen (Scintimun granulocyte) Disadvantage: production of HAMA (human antimurine antibody) alergic reaction before repeated examination - titer

99mTc- HMPAO WBC Indication: acute inflammatory conditions Inflammatory bowel disease infection of vascular or orthopedic prostheses

111In WBC 111In, T1/2 67h, 174, 247 keV, Indication: indolent conditions Chronic infections kidney infections

99mTc- HMPAO WBC 111In WBC Normal biodistrubion: liver, spleen, bone marrow, ( HMPAO genitourinary and gastrointestinal tracts )

67Gallium –citrate Several factors govern uptake: 67Ga , T ½ 78 h, γ rays (93,184, 296, 338 keV) Iron analog Several factors govern uptake: 1) Bind to transferrin in the plasma Increased blood flow and increased vascular membrane permeability result in increased delivery and accumulation in inflammatory foci 2) Bind to lactoferrin, which is present in high concetration in inflammatory foci 3) Bind to leukocytes 4) Direct uptake by bacteria - siderophore

67Gallium –citrate Imaging: 18-72 h Normal biodistribution: bone, bone marrow, liver, spleen, genitourinary and gastrointestinal tracts

67Gallium –citrate Indication: Vertebral osteomyelitis Immunocompromised patients Opportunistic respiratory tract infections

18FDG PET 18F, T ½ 110min, cyclotron produced glucose consumption inflammatory cells have an increased expresion of glucose transporters when they are activated. Cytokines and growth factors increase the affinity of glucose transporters for FDG. Imaging: 1 h Normal biodistrubion: , brain, liver, spleen, bone marrow

18FDG PET Indication: fever of undetermined origin vasculitis

IMAGING INDICATIONS Fever of Undetermined origin At least 3-wk duration, several episodes of fever exceeding 38,3ºC and no diagnosis after an appropriate evaluation 20 - 30% infection 15 - 25% neoplasms collagen vascular disease, granulomatous disease, cerebrovascular accidents

Fever of Undetermined origin Duration of illness: labeled leukocyte imaging is more sensitive early High negative predictive value for labeled leukocyte imaging, negative study excludes focal infection as the source of FUO. 18FDG, 67Ga citrate later + imaging of tumor

Fever of Undetermined origin 18FDG NHL sarkoidosis

Opportunistic Infection Do not incite a neutrophilic response Affect lungs 67Ga citrate

Opportunistic Infection 67Ga citrate diffuse uptake Pneumocystis carinii pneumonia

Postoperative Infection CT cannot always distinguish abscess from other fluid colection, tumor or normal postoperative changes Labeled WBC Labeled WBC accumulation through the left abdomen into the thigh – multiple abscesses were drained

Osteomyelitis 3F bone scintigraphy 3F bone scintigraphy + 67 Ga citrate 3F + WBC WBC + bone marow imaging with sulfur colloid

Osteomyelitis 3-phase bone scintigraphy: 99mTc MDP Bones not affected by underlying conditions high specificity Fractures, orthopedic hardware, neuropathic join - low specificity

3-phase bone scintigraphy + 67Ga citrate Osteomyelitis: 3-phase bone scintigraphy + 67Ga citrate Improved the specificity: distribution is spatially congruent but the relative intensity of uptake of 67Ga citrate is greater than that of the bone agent spinal OM : when MRI cannot be performed or is not diagnostic 99mTc MDP 67GA

Osteomyelitis: Labeled leukocytes do not accumulate at sites of increased bone mineral turnover in the absence of infection But inability to distinguish LL uptake from uptake in bone marrow Labeled leukocyte + bone marrow imaging with 99m Tc –sulfur colloid

Labeled leukocyte + bone marrow imaging with 99m Tc –sulfur colloid Both accumulate in the bone marow, only leukocytes accumulate in infection. Painful prosthesis – infection, aseptic loosening WBC bone marrow