European Nuclear Medicine Guide
99mTc]Tc-exametazine or [111In]In-oxine labelled leucocytes
An infection starts with colonization of tissue or organs by pathogenic exogenous noxae. In many cases, microorganisms are considered to be the cause of an infection. Tissues or organs react with an associated phenomenon, called acute inflammation. The presence of non-self-antigens or tissue degradation products activates mechanisms, such as the release of histamine and serotonin, increase of vascular permeability, hyper-expression of adhesion molecules on endothelial cells and secretion of chemotactic factors. All of these phenomena induce leukocyte rolling along the endothelium and migration of these leukocytes through the capillary wall.
White Blood Cells (WBCs) are isolated from the patient’s blood and labelled with [111In]In-oxine or [99mTc]Tc- exametazine ([99mTc]Tc-HMPAO). Either isolated granulocytes or mixed leucocytes can be used. Labelling of mixed leucocytes is preferred, despite the fact that this may cause higher uptake in the blood pool on the 4 h images due to the presence of labelled erythrocytes. The leucocytes are labelled with 111In-oxine or 99mTc- exametazine (99mTc-HMPAO). Autologous leucocytes are preferred as they are highly specific since they only accumulate as a consequence of active migration into infectious tissues. After intravenous reinjection, radiolabelled WBC show rapid clearance from the lungs and blood pool with progressive migration into the spleen, liver, bone marrow, and into sites of infection, where a neutrophilic infiltrate predominates. Radiolabelled WBCs are a specific indicator for leucocytic infiltration.
99mTc-labelled leucocytes have replaced 111In-labelled leucocytes for most indications because of their more optimal physical characteristics, availability, costs, and lower radiation burden. However, an advantage of [111In]In-leucocytes is, that there is no major kidney, bladder, or bowel excretion. In contrast, [99mTc]Tc-exametazine is released from the leucocytes which starts a few min after administration. Up to 7% per hour of the released 99mTc is excreted by the kidneys. The remainder is excreted by the liver and gut, thereby disturbing the imaging of the abdomen at 3 h post administration. Therefore, the use of 111In-leucocytes is preferred for evaluation of the kidneys, bladder, gall bladder, and intestines. For all other indications, 99mTc-leucocytes are preferable.
Depending on the indications, radiological imaging such as ultrasound, CT, and MRI play an important role and complemented by radionuclide imaging. Furthermore, for some indications FDG PET/CT may be the nuclear imaging modality of choice (e.g. patients with fever of unknown origin with low probability of infection, vascular graft infections, endocarditis). In patients with suspicion of osteomyelitis and in patients with suspected joint prosthesis infection (>2 years after placement of a hip prosthesis and >4 years after placement of a knee prosthesis) three phase bone scintigraphy with SPECT/CT may be the first choice.
The suggested activities to administer are:
In paediatric nuclear medicine, the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity to administer is 40 MBq 99mTc-labelledWhite Blood Cells. 111In-labelled WBC were not included in the paediatric dosage card, but the EANM guidelines indicate an administered activity per body weight of: 0.15-0.25 MBq/kg
The effective dose for 99mTc-WBC in adults is 11 µSv/MBq [3]. The organ with the highest absorbed dose is the spleen: 110 µGy/MBq.
The effective dose for 111In-WBC in adults is 360 µSv/MBq [109]. The organ with the highest absorbed dose is the spleen: 5.5 mGy/MBq (1).
The range in effective dose in adults for 99mTc-WBC is: 2.0-4.1 mSv per procedure.
The range in effective dose in adults for 111In-WBC is: 3.6-6.5 mSv per procedure.
Caveat: “Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."
Labelling of mixed leucocytes causes irradiation damage to the lymphocytes as a result of self-irradiation by low-energy Auger electrons. However, this damage is considered negligible.
Visual analysis: It is recommended to evaluate images without too many operator modifications (use decay-corrected images and display the images with the same intensity scale in total counts). Look at iliac bone (or sternum or skull) uptake at different time points as a reference region for bone marrow whenever possible.
Semi-quantitative analysis:
In summary:
The patient should fast prior to the examination in order to facilitate the isolation of leucocytes (better separation of WBC band and plasma). The patient may eat and drink again once the blood sample has been taken. Blood sample should be performed using a 19Gauge IV cannula to prevent haemolysis [361].
The potential interference of antibiotics with cell labelling has to be considered. The decision whether to perform or cancel the study due to antibiotic treatment depends on the clinical question and should be discussed case-by-case with the referring clinician.
During the labelling procedure, blood and blood elements from a patient, who could potentially be infected with pathogens, need to be handled with care. To prevent contamination of the operator who is performing the labelling, waterproof gloves should be worn throughout the procedure. Since the labelled leucocytes have to be re-injected into the patient, strict aseptic conditions are required for the labelling procedure. For this purpose, only sterile reagents and disposable plastic-ware should be used. Sterile gloves, cap and mask should be worn. Usually, the labelling of leucocytes is performed in a laminar flow cabinet or cell isolator, installed according to local regulations.
Simultaneous labelling of leucocytes from multiple patients is discouraged in order to prevent cross-contamination. Labelling of leucocytes from different patients should be carried out at physically separated locations unless closed devices are used. At all times correct identification of the patient’s blood products should be guaranteed. All syringes, tubes and other material which comes in contact with the patient’s blood components should be clearly labelled with the patient’s name, bar-code and/or with a colour code.
The detailed recommendations are available in the EANM Guidelines for the labelling of leucocytes with 111In-oxine and in the EANM Guidelines for the labelling of leucocytes with 99mTc-HMPAO [362,363].