Introduction

The indium 111- tagged white blood cell (WBC) scan is a type of imaging modality used to help identify regions of inflammation and thus infections when other imaging studies are equivocal or contraindicated.[1] Clinicians commonly use this test for diagnostic purposes in the evaluation of prosthetic joint infections, osteomyelitis, vascular graft infections, and fever of unknown origin.[1] The overall accuracy in diagnosing the infections above using indium 111-tagged WBC scan has widely ranged in the literature from sensitivity 60 to 100% and specificity 69 to 92%.[1] Briefly, white blood cells (WBCs) are obtained from a blood sample from a patient, are tagged with the radioisotope indium-111, and then re-injected intravenously into the patient. These labeled leukocytes localize to a region of inflammation visible on the whole body or regional nuclear imaging with bone scintigraphy.[1][2]

Specimen Collection

The patient’s blood is drawn in a vial and then placed in a centrifuge. This process will separate the plasma from red blood cells. It is essential to ensure that an anticoagulant such as heparin or acid citrate dextrose is used in the collection tube to prevent the blood from clotting.[2] The plasma is then again centrifuged to separate the platelet-rich plasma from the sample. The leukocytes are then obtained and suspended in a saline solution, and the application of the radiopharmaceutical 111-indium solution to the patient’s sample follows.[2] This solution is then re-injected into the patient. It is important to ensure appropriate personal protective safety equipment, aseptic technique, proper patient labeling, and the use of controls throughout the specimen collection process.[2][3]

Procedures

After the indium-labeled white blood cells are injected into the patient, the patient undergoes nuclear imaging.  The patient must be able to cooperate for roughly 60 minutes to obtain the imaging scans.[3] There is no special preparation required for the test. Approximately 1 to 2 hours after the sample is radiolabeled with the indium-111, it is re-injected into the patient.[3] Labeled WBCs that are stored greater than 3 hours before administration have decreased viability.[3] The administered recommended dose for adults is 0.3 to 0.5 mCi.[3] Further information regarding radiation dosing can be found in the "complications" section below.

Depending on the clinical situation, imaging is obtained at varying time intervals after administering the tagged white blood cells. It is most common to obtain imaging 1 to 4 hours after administration or 16 to 30 hours after, depending on the clinical situation.[3]

Indications

111-Indium white blood cell scan may be utilized to detect and localize the site of infection and to correlate clinically with the patient presentation of various pathologic processes, including [2]:

• Osteomyelitis not involving the spine (radionucleotide scans utilizing gallium have been shown to be superior to indium alone in detecting osteomyelitis of the spine).[4]
• Prosthetic joint infection 
• Vascular grafts
• Intra-abdominal infections
• Abscesses
• Endocarditis
• Foot ulcers
• Infected implanted devices such as central venous catheters
• Fevers of unknown origin when there is a high probability of infection
• Inflammatory bowel disease

Potential Diagnosis

All of the indications mentioned above are potential diagnoses that are potentially obtainable from the utilization of a 111-indium white blood cell scan.[2] The use of 111-indium tagged white blood cell scans also requires cooperation and effective communication between the entire multidisciplinary team to maximize patient outcomes.[5] Radionulcleotide scans alone are typically not sufficient as a solitary test but best interpreted and used in conjunction with the patient’s specific presentation.[1]

Normal and Critical Findings

Interpretation of a radionucleotide labeled leukocyte study requires knowledge of normal and abnormal variants. Normal findings at 18 to 24 hours of the study include uptake primarily by the reticuloendothelial system of the spleen, liver, and bone marrow.[3] Diffuse pulmonary activity occurs up to 4 hours after injection, and this is a normal finding.[3]

When detecting an abscess, the uptake in that pathologic area may have uptake either greater than or equal to the uptake of the liver. Up to one-half of the cases can be visualized four hours after injection, with greater than 90% uptake by 24 hours.[3]

In cases of osteomyelitis, radiolabeled indium-111 uptake significantly increases. However, if a patient has been receiving treatment with IV antibiotics before obtaining a nuclear scan with radiolabeled indium, the results may show limited uptake in that area, producing a false negative result.[3]

In cases of infected orthopedic hardware, the indium 111- tagged leukocyte scan shows uptake that usually increases in the area of interest. However, in the presence of orthopedic hardware or a prosthesis, it may make radiological interpretation difficult as the orthopedic device displaces bone marrow.[3] In this case, it may be necessary to compare and localize the area of interest with a 99mTc-sulfur SPECT, as acute infection may have high uptake on the 111-indium WBC scan with discordant activity on a 99m-Tc-sulfur study.[3]

Interfering Factors

There are potential false positives and false negatives during the interpretation of a 111-indium leukocyte scan. There is the possibility for localization of uptake in instances unrelated to infection.[1] These include an accessory spleen, acute bleed/hematomas, neoplasms, foreign body inflammatory response, and inflammatory bowel disease.[3] Noninfectious etiologies of increased uptake on 111-indium nuclear scans include rheumatoid and gouty arthritis, which may also lead to false-positive interpretations.[3] When concerned with infectious etiologies of the gastrointestinal tract, it is important to note that the labeled 111-indium WBC scan does not accumulate in normal bowel.[3] This contrasts to the 99mTc labeled scan, thus potentially producing a false positive result during the interpretation of the indium 111- tagged leukocyte nuclear scan.[6]

Pathologic disease processes including chronic abscess, any lymphocytic mediate infection such as sarcoidosis or tuberculosis, and hepatic or splenic abscess given these organs uptake 111 indium to metabolize may cause false-negative nuclear scans with 111- indium.[3] 

Given the numerous false positive and false negative interpretations of the 111-indium WBC labeled nuclear scan, correlating clinically to a specific patient's history and physical exam, as well as previously obtained imaging studies, is extremely important.[1][3]

Complications

A complication of a 111-indium white blood cell scan is radiation exposure, mostly affecting the organs that metabolize the indium, such as the spleen, liver, and bone marrow.[3] The average effective dose of radiation for nuclear medicine procedures ranges from 0.3 to 20 mSv.[7] The recommended dose per year is no greater than 50 mSv.[7] A tagged WBC scan with indium on average is nearly equivalent to a chest CT scan.[7] There are recommended dosing of 0.3 to .5 mCi for adults.  For pediatric patients, the recommended radiation dose is weight-based at 0.004 to 0.007 mCi/kg. Therefore, the clinical utility of obtaining a 111-indium labeled white blood cell scan should clearly be indicated, and the clinician should have a discussion with the patient.[3]

Patient Safety and Education

Before obtaining a radiolabeled nuclear scan with indium, it is essential to discuss the clinical utility, radiation exposure, and overall process of a 111-indium WBC scan with patients. 

Clinical Significance

The indium 111- tagged white blood cell (WBC) scan is used to help identify regions of inflammation and thus infections when other imaging studies are equivocal or contraindicated.[1] In addition to a 111-indium WBC scan, the gallium 67 radiolabeled scan has been used previously as a type of nuclear imaging scan.[8] However, gallium 67 scans may require up to 72 hours of waiting from the time of injection to the time of nuclear imaging, further delaying potential treatment of suspected infection.[8] Compared to the Gallium 67 radionucleotide scans, 111-indium have superior specificity in the setting of osteomyelitis, fever of unknown origin, and prosthetic joint infections.[1] For patients with suspected prosthetic joint infection, vascular grafts, intra-abdominal infections, abscesses, endocarditis, foot ulcers, infected implanted devices such as central venous catheters, fevers of unknown origin when there is a high probability of infection, and Inflammatory bowel disease, sensitivity, and specificity has ranged from 60 to 100% and 69 to 92%, respectively.[1][9][10] A radiolabeled white blood cell scan with indium used in the appropriate clinical setting has well-documented clinical utility.