Joint Program in Nuclear Medicine

Gallium-67 for Infection / Inflammation

John P. Kalabat, MD
Rachel A. Powsner, MD

January 6, 2004

Presentation

An 86 year-old man with recent left femoropopliteal bypass graft and endarterectomy presented with methicillin resistant staphylococcus aureus (MRSA) bacteremia and abdominal pain.

Imaging Findings

Planar images in the anterior (ant) and posterior (post) projection with spot views, and SPECT images (axial slices, coronal slices, and sagital slices) from 48 hour post injection gallium show increased uptake in the lower thoracic spine (shown by arrow on the planar images). On a T2-weighted MRI, high signal (white) at the disc and adjacent vertebral bodies compatible with discitis with adjacent osteomyelitis.

Diagnosis

Vertebral Osteomyelitis

Discussion

Radiochemistry

Gallium-67 citrate is produced by a cyclotron. Charged particle bombardment of enriched Zn-68 is used to produce gallium-67. The gallium-67 is then complexed with citric acid to form gallium citrate. The half life of gallium-67 is 78 hours. It decays by electron capture. The target organ is large bowel.

Gallium-67 photopeaks:

Energy	Abundance
93 keV	40%
184 keV	20%
300 keV	17%
393 keV	5%

Physiology

Ga-67 acts as an iron analogue. Initially it binds to transferrin. Assuming adequate blood flow, the complex diffuses through loose endothelial junctions of capillaries at sites of inflammation and enters the extracellular fluid. Leukocytes migrate to sites of inflammation and degranulate, releasing large quantities of lactoferrin.

Ga-67 has higher affinity for lactoferrin than transferrin. Ga-67 also attaches to siderophores of bacteria. Therefore can be used in leukopenic patients with bacterial infection and in detecting sterile abscesses that provoke a leukocyte response.

10% to 25% of the dose of gallium-67 is excreted within 24 hours after injection (the majority of which is excreted through the kidneys). After 24 hours the principal excretory pathway is colon.

Areas where Ga-67 normally localizes include:

liver (site of highest uptake)
bone marrow
spleen
salivary glands
nasopharynx
lacrimal glands
breast uptake (especially in pregnant and lactating women)
kidneys and bladder in the first 24 hours - faint uptake can still be normal for up to 72 hours
mild diffuse lung uptake at 24 hours or less

Tissue distributions in children which differ from those in adults:

growth plates
spleen
thymus

Technique

Common injection doses range from 3-6 mCi. Imaging should not usually be sooner than 24 hours - high background at this time produces false negatives.

Forty-eight hour whole body images are appropriate. Delayed imaging can be obtained even 1 week or longer after injection if bowel is confounding. SPECT can be performed as needed. Oral laxatives or enemas can be given before imaging to reduce bowel activity and reduce dose to large bowel; however, the usefulness of bowel preparation is controversial.

Common Indications of gallium-67 imaging

Whole-body survey to localize source of fever in patients with Fever of Unknown Origin (FUO).
Detection of pulmonary and mediastinal inflammation/infection, especially in the immunocompromised patient.
Evaluation and follow-up of active lymphocytic or granulomatous inflammatory processes such as sarcoidosis or tuberculosis.
Diagnosing vertebral osteomyelitis and/or disk space infection where Ga-67 is preferred over labeled leukocytes.
Diagnosis and follow-up of medical treatment of retroperitoneal fibrosis.
Evaluation and follow-up of drug-induced pulmonary toxicity (e.g. Bleomycin, Amiodarone)
Evaluation of patients who are not candidates for WBC scans (WBC count less than 6,000 and/or poor IV access).

Osteomyelitis:

When osteomyelitis is suspected, a gallium scan is most helpful when used in conjunction with a bone scan. A gallium scan is considered positive when uptake or distribution of gallium is greater than or equal to bone scan uptake. Congruent uptake is equivocal for the diagnosis. False positive diagnosis for osteomyelitis can be seen in acute inflammatory joint disease due to WBC reaction. The sensitivity and specificity for chronic osteomyelitis is lower than for acute osteomyelitis.

Comparison to labeled WBC's for diagnosing osteomyelitis:

Labeled WBC's are generally preferred for osteomyelitis and prosthesis infection.
Gallium imaging is superior to labeled WBC's in vertebral and disc space infections.
Gallium is technically more feasible in patients with poor venous access.

Diagnosis of lung disease:

48 hour images should be used for diagnosis of lung disease since healthy people can have faint uptake in the lungs in the 24 hour images. Gallium avidity (not including neoplasms) is seen with infection and inflammation (including interstitial and granulomatous diseases).

Lung uptake in immunosuppressed/AIDS patients:

The following is a useful guide for common (but not the only) differentials for varying patterns of lung uptake in immunosuppressed/AIDS patients:

Focal uptake:

Bacterial pneumonia likely

Diffuse and intense uptake (greater than liver):

Diffuse and less intense uptake:

PCP
CMV
MAI
Interstitial pneumonitis

Nodal uptake:

TB
MAI
Lymphoma

No uptake and negative CXR:

No infection

No uptake and positive CXR:

Kaposi's sarcoma should be considered

Pulmonary toxicity uptake occurs with a variety of chemotherapeutic agents and other drugs including:

amiodarone
bleomycin
busulfan
nitrofurantoin
nitrosurea
cyclophosphamide
methotrexate

Uptake can occur despite negative CXR. Uptake is usually diffuse. Uptake can also correlate with a radiation port in radiation induced pulmonary toxicity.

Sarcoidosis:

When it occurs, pulmonary uptake in sarcoidosis can be diffuse. The amount of pulmonary uptake correlates with granuloma formation. There is a close correlation between the percentage of uptake of gallium in the lungs and the increase of the vital capacity after therapy with corticosteroids. The panda sign indicates symmetric increased radiotracer uptake in the parotid, lacrimal, and submandibular glands.

The lambda sign indicates right paratracheal, parahilar, and infrahilar lymph node uptake. The combination of lambda and panda signs or panda sign with bilateral symmetrical hilar lymphadenopathy on chest X-ray are both very specific for sarcoidosis.

Retroperitoneal fibrosis:

There is a correlation between the clinical symptoms, the surgical and histologic findings, the activity of the disease and the results of Ga-67 scintigraphy. Retroperitoneal fibrosis without gallium uptake is probably mature, with few inflammatory elements. Gallium imaging may be useful in identifying the most active sites of disease for possible biopsy and for subsequent monitoring of response to therapy.

Fever of unknown origin:

If no recent surgery has been performed, gallium is preferable to labeled cells. Recent surgery makes infectious cause for the fever more likely, for which labeled WBC's are preferable. Without a recent surgery, neoplastic cause of unknown fever is a possibility, for which Gallium is better suited.

Abdomen/pelvis:

Sulfur colloid study may be a useful adjunct to gallium imaging to diagnose intrahepatic abscesses. Diagnosing renal inflammatory or infectious disease should be made 48 hours unless activity is obviously asymmetric. Peritonitis can be suggested with diffuse activity throughout abdomen, esp. if it extends laterally to right lobe of liver and right subdiaphragmatic region. Diagnosing colitis may be challenging secondary to normal physiologic localization of gallium.

References

Christopher J. Palestro, Charito Love, Gene G. Tronco, and Maria B. TomasRole of Radionuclide Imaging in the Diagnosis of Postoperative InfectionRadioGraphics 2000; 20: 1649-1660.
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Abe S, Munakata M, Nishimura M, Tsuneta Y, Terai T, Nakano I, Ohsaki Y, Kawakami Y. Gallium-67 scintigraphy, bronchoalveolar lavage, and pathologic changes in patients with pulmonary sarcoidosis.Chest. 1984 May;85(5):650-5.
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Hillebrand M, Gerstenberg E, Kuntz RM, L'age M, Grosse G. [67Ga scintigraphy in retroperitoneal fibrosis (RPF): indications, application and clinical relevance--report of five patients]Nuklearmedizin. 1996 Feb;35(1):25-30. German.
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Society of Nuclear Medicine Procedure Guidelinefor Gallium Scintigraphy in Inflammation http://www.snm.org/pdf/infga2.pdf

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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu