Immunoscintigraphy

Immunoscintigraphy is a diagnostic procedure used in nuclear medicine to detect the accumulation of radioactively labeled antibodies, for example, in tumors or sites of inflammation. Antibodies or immunoglobulins (Ig) are physiologically produced by plasma cells (special B lymphocytes) as part of the specific immune defense and are used to recognize antigens (e.g. surface structures of pathogens). In general, immunoglobulins are structured according to the same basic pattern, but contain a highly variable part for antigen binding. Due to this variability, very different pathogens or even endogenous target structures can be recognized as antigens. Antibody formation against endogenous structures is relevant in the context of autoimmune diseases. For research as well as for clinical application (e.g. diagnostics such as immune scintigraphy), the generation of pure monoclonal antibodies (derived from a cell clone and thus directed only against a specific antigen) is of great importance. Plasma cells are taken from the body, activated with desired antigens and fused with B-lymphocyte tumor cells. Through appropriate selection steps, cells can finally be grown to produce the required antibody. Immunoscintigraphy uses artificially produced antibodies or their fragments (Fab’), which are radioactively labeled with various tracers (e.g. 99mTc, 123I, 111In) and administered to the patient. Depending on the target structure, the antibodies attach to specific cells and can be registered by their radioactive component using, for example, a gamma camera.

Indications (areas of application)

  1. Oncological issues (tumor diagnostics): the use of monoclonal antibodies or their fragments is based on the principle that the antibodies are directed against specific antigens on the surface of tumor cells. Antibody binding is very tumor type specific and so far limited to only a few tumor entities (tumor type or cancer property). Histology (fine tissue examination) and the detection of specific hormones or tumor markers determine the indication. Examples:
  • 99mTc-labeled CEA antibody: This antibody can be used to detect local recurrences (recurrence of tumor disease at the same site) of rectal/sigmoid carcinoma (rectum = rectum; sigma is the part of the colon localized on the left side that merges into the rectum).
  • 123I- or 111In-labeled anti CD20 antibodies: these antibodies are used in CD20-positive non-Hodgkin’s lymphoma (NHL; malignant diseases of the lymphatic system; malignant lymphomas). Here, scintigraphy is particularly indicated for planning radioimmunotherapy (e.g., calculation of the radiation dose during therapy).

2. inflammation scintigraphy.

  • Specific enrichment: 99mTc-labeled monoclonal antigranulocyte antibodies label the surface antigens of granulocytes (called neutrophils; these are the most abundant leukocytes (white blood cells), accounting for 50-65% of the total; as phagocytes (scavenger cells), they are part of the innate immune defense) after injection, thus demonstrating a granulocytic inflammatory response. Some of the antibodies still bind to circulating granulocytes and therefore migrate cell-bound to the inflammatory focus. Another part of the antibodies reaches the inflammatory area directly due to the increased perfusion (blood flow) and increased capillary permeability (permeability of the small blood vessels) and binds locally to the already migrated granulocytes. The radiopharmaceutical is indicated for acute inflammation.
  • Nonspecific accumulation: 99Tc-labeled human immunoglobulin (HIG) is accumulated in the inflammatory focus via increased capillary permeability and retention. There is no specific binding to granulocytes or other inflammatory cells. The radiopharmaceutical is indicated in chronic inflammation or the clarification of chronic febrile conditions.

Contraindications

Relative contraindications

  • Lactation phase (breastfeeding phase) – breastfeeding must be interrupted for 48 hours to prevent risk to the child.
  • Repeat examination – no repeat scintigraphy should be performed within three months due to radiation exposure.

Absolute contraindications

  • Gravidity (pregnancy)

The procedure

  1. The radiopharmaceutical is applied intravenously.
  2. Subsequently, a waiting period must be observed until the radiolabeled antibody reaches/into the tumor cell or inflammatory focus. In addition, for successful scintigraphy, a favorable target-background relation must be established, i.e., the specific radioactivity accumulation in the tumor or inflammatory focus must stand out clearly from the nonspecific background radiation. The time interval between injection and the scintigraphic image depends on the radiopharmaceutical used. In the meantime, no separate radiation protection measures need to be taken due to the only low radiation intensity, so the patient can attend other appointments during the waiting time. Examples:
    • 99mTc-monoclonal CEA antibodies: scintigraphy after 6 and 24 hours.
    • 111In-monoclonal anti-CD20 antibodies: scintigraphy at 1, 24, 48, 72 and 144 hours.
  3. For the acquisition of radioactivity or preparation of the scintigraphy, gamma cameras are used as a planar technique (representation in one plane with superimpositions) or slice imaging systems (single photon emission computed tomography, SPECT) for superimposition-free imaging of particularly relevant body sections.

Possible complications

  • Intravenous application of radiopharmaceutical may result in local vascular and nerve lesions (injuries).
  • Radiation exposure from the radionuclide used is rather low. Nevertheless, the theoretical risk of radiation-induced late malignancy (leukemia or carcinoma) is increased, so that a risk-benefit assessment should be performed.