Applied Radiology

Gallium-67 citrate (Ga-67) has been used in the localization of multipletumors, most notably lymphoma, hepatocellular carcinoma, and melanoma. Becauseits behavior is similar to that of the ferric ion, it is accumulatedintracellularly within tumor cells. Like the ferric ion, Ga-67 binds totransferrin and enters the extracellular fluid space, after which it is boundby transferrin receptors on the tumor cell surface. The levels of transferrinreceptor expression tend to be increased with higher grade lymphomas,corresponding to increased uptake by these tumors.1 Once Ga-67 been transportedinto the cell, it is bound to the iron-binding proteins-ferritin andlactoferrin-and ultimately stored within intracellular lysosomes. Both of theseproteins are found in increased concentration within tumor cells, accountingfor the increased uptake of gallium in tumor versus normal cells. Thedistribution of gallium within normal structures includes the liver, lacrimaland salivary glands, spleen, bone, and bone marrow. Additionally, there hasbeen significant activity noted within the bowel. During the first 24 hoursfollowing injection, excretion is from the genitourinary tract as well as thegastrointestinal tract; however, this changes to primarily bowel excretionafter the first 24 hours.

The use of Ga-67 in the evaluation of tumors has been limited, to some extent,by technological and physiologic factors. Early studies have underestimated thesensitivity and specificity of gallium tumor detection by the use of outdatedtechnologies. To a large degree, these technological limitations have beenminimized with the advent of SPECT imaging and improved imaging protocols.Recent studies have demonstrated increased sensitivity and specificity with theutilization of these newer imaging techniques.2,3

Physiological limitations have existed as well, and these continue to causeproblems in the routine utilization of gallium for tumor detection. Mostnotably, the significant uptake of gallium by the GI tract has limited the useof this agent in the evaluation of abdominal tumors. Some authors haveadvocated the use of cleansing enemas prior to imaging. At our institution, wehave not found this helpful and have found the irritation to the bowel by thesepreparations offsets any advantage gained by their routine use. Anotherphysiologic factor which has limited the routine use of gallium has been thevaried uptake by tumor cells. While some tumors demonstrate marked galliumavidity, other tumors of the same cell type have not. Furthermore, the avidityof a metastatic lesion may not reflect that of the original tumor mass.Nevertheless, clinical applications for the use of gallium exist.

Perhaps the area in which gallium has been most useful is the follow-up ofknown gallium avid lymphoma after radiation or chemotherapy. Follow-up of knowntumor masses with CT, the commonly accepted methodology, may demonstrateresidual mass at the site of previously known lesions. While CT is unable todistinguish between residual or recurrent tumor versus fibrosis, gallium isquite useful in making this distinction. Non-active scar tissue (fibrosis) willnot accumulate gallium, while recurrent or residual lymphoma will. In patientswith complete remission, gallium imaging was reported to be negative in 95% ofpatients, compared with 57% on CT and 55% on chest radiographs.2,3 While only20% of patients may have enlargement of the mediastinum, gallium scans haverevealed increased tracer accumulation in 100% of the patients who relapsed.Other studies have shown the specificity of gallium imaging for residualdisease at 93% compared with 83% for MRI.4 This distinction is further aided bythe initial acquisition of a pre-treatment gallium scan to determine avidity.Clearly, the implications of a negative gallium scan are less clear than thoseof a positive gallium follow-up. Because of this, the follow-up evaluationshould be done after definitive chemotherapy and consolidation radiotherapy.
At our institution, a 10 mCi dose of Ga-67 is injected intravenously, followedby planar imaging started at 48 hours. Additional imaging is performed at 72and 96 hours, or longer, if needed. SPECT imaging is performed, at the abovetimes, of those areas most suspected of harboring viable lymphoma.

A negative scan may indicate the presence of scar or a change in the avidity ofthe original tumor mass. While this finding does not carry as clear aninterpretation as a positive scan, it is supportive evidence of fibrosisfollowing radiation or chemotherapy. Definitive diagnosis in this case willdepend upon needle biopsy, which may be deferred to later follow-up based onthe clinical presentation of the patient. Conversely, a positive post-treatmentscan is consistent with a recurrent or residual tumor. It should be noted thatthymic rebound causing benign increased accumulation of gallium can occurduring or immediately after chemotherapy and is one cause of false-positiveexaminations. Other benign causes such as respiratory tract infections andsarcoidosis also should be considered.

Images from two patients are included here. Figures 1A and 1B demonstrate apatient with a positive CT scan and a negative gallium scan, consistent withscar tissue. Figures 2A and 2B demonstrate a patient with a positive CT and apositive gallium scan, consistent with active disease. AR