Equis ISSN 2398-2977

Infection / inflammation: scintigraphy

Synonym(s): Scintigraphic imaging of infection and inflammation, labeled white cell scans

Contributor(s): Russel Malton, Rachel Murray

Introduction

  • Scintigraphic methods used to detect foci of inflammation rely on the radiolabeling of  blood constituents which target and participate in the inflammatory process. The universal constituent used to date has been the leukocyte.
  • Radiolabeling leukocytes without affecting cell viability and function has allowed scintigraphic detection of sites of accumulation.  The procedure is not specific for detection of bacterial infection because many disease processes are associated with an inflammatory response, including neoplasia.
  • Inflammatory conditions which have been imaged using labeled leukocyte scintigraphy include, acute and chronic osteomyelitis   Spine: osteomyelitis  , diskospondylitis, intra-abdominal sepsis/abscesses   Abdomen: abscess  , inflammatory bowel disease   Chronic inflammatory bowel disease  , acute and chronic pyelonephritis, myocardial inflammation following infarction, vascular graft infections, skeletal metastases and pyrexia of unknown origin (PUO).
  • With the development of newer technologies, labeled leukocyte scintigraphy has been outdated as a diagnostic tool for investigating a number of the above conditions in man. It however remains important for imaging inflammatory bowel disease and musculoskeletal sepsis.

Radiopharmaceuticals used to label leukocytes

99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO)

  • Originally developed for cerebral blood flow studies in man. Due to its lipophilic nature it was found to successfully label leukocytes.  It is the most commonly used radiopharmaceutical for leukocyte labeled studies in the horse.
  • Advantages of use:
    • Technetium has superior imaging characteristics. The photon energy is more suited to gamma camera imaging   →   greater spatial resolution. The higher photon flux eliminates the need for long acquisition times.
    • More selective labeling of granulocytes than monocytes.
    • Ability to label leukocytes in the presence of plasma which inhibits premature leukocyte activation.
    • Wide availability and relative low cost of technetium allows higher initial activity to be used for labeling. This helps counter the poorer labeling efficiency of 99mTc-HMPAO.
  • Disadvantages of use:
    • Urinary tract excretion of 99mTc-complexes and potential hepatobiliary excretion   →   gastrointestinal uptake.
    • The reconstituted radiopharmaceutical is also unstable and must be labeled within 30 min of reconstitution.  Various additives have been used to extend the shelf life of the technetium eluate.  

111Indium-oxine (111In-oxine)

  • The first radiopharmaceutical used in leukocyte labeled studies in man. Only one study using this radiopharmaceutical in a horse has been documented in the literature. 
  • Advantages of use:
    • 111In-oxine has a higher labeling efficiency and higher label retention. 
    • The longer half-life (67 h) is considered an advantage for imaging chronic inflammation, however neutrophils have an average circulation time of only 10-12 h with the result that localization of labeled leukocytes at the site of an inflammatory focus is completed by 24 h.  Further delayed imaging is therefore unlikely to provide additional information.
  • Disadvantages of use:
    • The higher photon energy of the emissions requires special collimators which often have poor spatial resolution.
    • The low photon flux necessitates longer acquisition times risking poor image quality due to patient movement.
    • The high cost per unit dose may limit the dosage used, further influencing image quality. 
    • The longer half-life imposes a time delay for patient release.
    • Other radiolabeled products are used to image inflammation. A number of these are the focus of continued research:
      • 99mTc-human polyclonal immunoglobulin (99m Tc- HIG)
      • Monoclonal anti-leukocyte antibodies
      • Monoclonal antibodies to activated endothelium
      • 99mTc-Dextran
      • 99mTc-citrate
      • Chemotactic peptides
      • 99mTc-interleukin-8
      • 99mTc-ciprofloxacin (infecton)
    • The diagnostic value of several of these inflammation seeking agents is affected by low target to background ratios.

Dosage

  • Optimal radioactivity doses for labeled leukocyte studies in the horse have not been validated and large dose ranges have been reported for 99mTc-HMPAO (1-10 MBq/kg BW).
  • Adult: 1.1-1.3 GBq (30-35 mCi) - likely to provide satisfactory count densities. The count densities achieved also depend somewhat on labeling efficiency and time of scan post-injection.
  • 111In-oxine: radioactivity of 11.1-37 MBq (0.3 to 1.0 mCi) is typically used at the time of radiolabeling. Dosage not reported.

Uses

  • Localization of the site(s) of suspected sepsis in a septicemic neonate or lame foal which has an inflammatory blood picture, but where neither clinical nor radiological investigation has revealed a site of infection.
  • To determine whether lesions identified on clinical examination or by other diagnostic techniques involve significant inflammation or sepsis, eg radiological lucencies or opacities.
  • Evaluation of post-operative patients with pyrexia or persistent pain or swelling. The strongest indication is in orthopedic patients with suspected sepsis of a healing fracture or the site of an orthopedic implant. Bone scan is less likely to distinguish normal fracture healing from infection in such cases.
  • Diagnosis of inflammatory bowel disease.
  • To monitor progression or response to therapy of an identified inflammatory or septic condition.
  • Investigation of pyrexia of unknown origin.

Investigation in previously well patients by labeled leukocyte scintigraphy is considered of questionable value as many of these are caused by non-infective pathology or non-pyogenic organisms.

Advantages

  • Labeled leukocyte scintigraphy is a potentially sensitive non-invasive method to localize a site of  inflammation or infection and monitor the response to treatment.

Disadvantages

  • Low specificity and sensitivity for infection.
  • Expensive and time consuming.
  • Poor labeling efficiency will adversely affect the scan.
  • Limited number of studies in the horse and varying degrees of  reported normal distribution of leukocytes complicates interpretation.
  • Hepatobiliary and urinary excretion of  99mTc-complexes may affect evaluation of gastrointestinal and urinary tract.
  • Must have authorization to receive and dispose of radioactive substances.

Requirements

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Preparation

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Procedure

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Aftercare

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • East L M, Trumble T N, Steyn et al (2000) The application of technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO) labeled white blood cells for the diagnosis of right dorsal ulcerative colitis in two horses. Vet Radiol 41 (4), 360-364 PubMed.
  • Long C D, Galuppo L D, Waters N K & Hornof W J (2000) Scintigraphic detection of equine orthopedic infection using Tc-HMPAO labeled leukocytes in 14 horses. Vet Radiol 41 (4), 354-359 PubMed.
  • Weller R & Marr C M (2000) Nuclear scintigraphy with 99mTc-HMPAO labeled leukocytes in the assessment of horses with malabsorption. In:Abstracts of ACVR.Vet Radiol 41 (6), 564.
  • Peters A M (1995) Imaging infection and inflammation in veterinary practice. Equine Vet J 27 (4), 242-244 PubMed.
  • Butson R J, Webbon P M & Fairbairn S M (1995) 99Tcm-HMPAO labeled leukocytes and their biodistribution in the horse: a preliminary investigation. Equine Vet J 27 (4), 313-315 Wiley Online Library.
  • Lattimer J C, Reed A L & Johnson P J (1995) Preliminary results of  99mTc HMPAO labeled leukocyte scintigraphy in horses. In:Abstracts of ACVR.Vet Radiol 36 (4), 363.
  • Daniel G B, Tucker R L, Buckman T & Daniel S L (1992) In vitro comparison of equine granulocytes labeled with 99mTc-hexamethylpropyleneamine oxime or 111In-oxine. Am J Vet Res 53 (6), 871-875 PubMed.
  • Koblik P D, Lofstedt J, Jakowski R M et al (1985) Use of 111In-labeled autologous leukocytes to image an abdominal abscess. JAVMA 186 (12), 1319-1322 PubMed.

Other sources of information

  • Ellis B L & Sampson C B (1999)Radiolabeling of blood cells-theory and practice.In:Textbook of Radiopharmacy.3rd edn. Gordon & Breach Science, Amsterdam, The Netherlands. pp 83-104.


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