Gallium scan

Nuclear medicine test that uses gallium to obtain images of tissues

A gallium scan is a type of nuclear medicine test that uses either a gallium 67 (67Ga) or gallium 68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Gallium can also be used in other forms, for example 68Ga PSMA is used for cancer imaging. The gamma emission of gallium 67 is imaged by a gamma camera, while the positron emission of gallium 68 is imaged by positron emission tomography (PET). Gallium salts are taken up by tumors, inflammation, and both acute and chronic infection, allowing these pathological processes to be imaged. Gallium is particularly useful in imaging osteomyelitis that involves the spine, and in imaging older and chronic infections that may be the cause of a fever of unknown origin. Gallium 68 DOTA scans are increasingly replacing octreotide scans (a type of indium 111 scan using octreotide as a somatostatin receptor ligand). The gallium 68 is bound to an octreotide derivative chemical such as DOTATOC and the positrons it emits are imaged by PET CT scan. Such scans are useful in locating neuroendocrine tumors and pancreatic cancer.

In the past, the gallium scan was the gold standard for lymphoma staging, until it was replaced by positron emission tomography (PET) using fludeoxyglucose (FDG). Gallium imaging is still used to image inflammation and chronic infections, and it still sometimes locates unsuspected tumors as it is taken up by many kinds of cancer cells in amounts that exceed those of normal tissues. Thus, an increased uptake of gallium 67 may indicate a new or old infection, an inflammatory focus from any cause, or a cancerous tumor. It has been suggested that gallium imaging may become an obsolete technique, with indium leukocyte imaging and technetium antigranulocyte antibodies replacing it as a detection mechanism for infections. For detection of tumors, especially lymphomas, gallium imaging is still in use, but may be replaced by fludeoxyglucose PET imaging in the future. In infections, the gallium scan has an advantage over indium leukocyte imaging in imaging osteomyelitis (bone infection) of the spine, lung infections and inflammation, and for chronic infections. In part this is because gallium binds to neutrophil membranes, even after neutrophil death. Indium leukocyte imaging is better for acute infections (where neutrophils are still rapidly and actively localizing to the infection), and also for osteomyelitis that does not involve the spine, and for abdominal and pelvic infections. Both the gallium scan and indium leukocyte imaging may be used to image fever of unknown origin (elevated temperature without an explanation). However, the indium leukocyte scan will image only the 25% of such cases which are caused by acute infections, while gallium will also localize to other sources of fever, such as chronic infections and tumors.

The body generally handles Ga3+ as though it were ferric iron (Fe III), and thus the free isotope ion is bound (and concentrates) in areas of inflammation, such as an infection site, and also areas of rapid cell division. Gallium (III) (Ga3+) binds to transferrin, leukocyte lactoferrin, bacterial siderophores, inflammatory proteins, and cell membranes in neutrophils, both living and dead. Lactoferrin is contained within leukocytes. Gallium may bind to lactoferrin and be transported to sites of inflammation, or binds to lactoferrin released during bacterial phagocytosis at infection sites (and remains due to binding with macrophage receptors). Gallium 67 also attaches to the siderophore molecules of bacteria themselves, and for this reason can be used in leukopenic patients with bacterial infection (here it attaches directly to bacterial proteins, and leukocytes are not needed). Uptake is thought to be associated with a range of tumour properties including transferring receptors, anaerobic tumor metabolism and tumor perfusion and vascular permeability.

Whole body survey to localize source of fever in patients with fever of unknown origin. 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 gallium 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). Note that all of these conditions are also seen in PET scans using the gallium 68.

The main (67Ga) technique uses scintigraphy to produce two dimensional images. After the tracer has been injected, images are typically taken by a gamma camera at 24, 48, and in some cases, 72, and 96 hours later. Each set of images takes 30–60 minutes, depending on the size of the area being imaged. The resulting image will have bright areas that collected large amounts of tracer, because inflammation is present or rapid cell division is occurring. Single photon emission computed tomography (SPECT) images may also be acquired. In some imaging centers, SPECT images may be combined with computed tomography (CT) scan using either fusion software or SPECT/CT hybrid cameras to superimpose both physiological image information from the gallium scan, and anatomical information from the CT scan. A common injection dose is around 150 megabecquerels. Imaging should not usually be sooner than 24 hours as 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.

The positron emitting isotope, 68Ga, can be used to target prostate specific membrane antigen (PSMA), a protein which is present in prostate cancer cells. The technique has been shown to improve detection of metastatic disease compared to MRI or CT scans. In December 2020, the U. S. Food and Drug Administration (FDA) approved 68Ga PSMA 11 for medical use in the United States. It is indicated for positron emission tomography (PET) of prostate specific membrane antigen (PSMA) positive lesions in men with prostate cancer.

Gallium PSMA scanning is recommended primarily in cases of biochemical recurrence of prostate cancer, particularly for patients with low PSA values, and in patients with high risk disease where metastases are considered likely.

An intravenous administration of 1.8–2.2 megabecquerels of 68Ga PSMA 11 per kilogram of bodyweight is recommended. Imaging should commence approximately 60 minutes after administration with an acquisition from mid thigh to the base of the skull.

68Ga DOTA conjugated peptides (including 68Ga DOTA TATE, DOTA TOC and DOTA NOC) are used in positron emission tomography (PET) imaging of neuroendocrine tumours (NETs). The scan is similar to the SPECT octreotide scan in that an octreotide based somatostatin analogue (such as edotreotide) is used as the radioligand, and there are similar indications and uses as ocreotide scans, however image quality is significantly improved. Somatostatin receptors are overexpressed in many NETs, so that the 68Ga DOTA conjugated peptide is preferentially taken up in these locations, and visualised on the scan. As well as diagnosis and staging of NETs, 68Ga DOTA conjugated peptide imaging may be used for planning and dosimetry in preparation for lutetium 177 or yttrium 90 DOTA therapy. In June 2016, Netspot (kit for the preparation of gallium Ga 68 dotatate injection) was approved for medical use in the United States. In August 2019, 68Ga edotreotide injection (68Ga DOTATOC) was approved for medical use in the United States for use with PET imaging for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adults and children. The U. S. Food and Drug Administration (FDA) approved 68Ga edotreotide (DOTATOC) based on evidence from three clinical trials (Trial 1/NCT#1619865, Trial 2/NCT#1869725, Trial 3/NCT#2441062) of 334 known or suspected neuro endocrine tumors. and as Netvision in May 2022.

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, then emits de excitation gamma rays that are detected by a gamma camera. Primary emission is at 93 keV (39% abundance), followed by 185 keV (21%) and 300 keV (17%). For imaging, multiple gamma camera energy windows are used, typically centred around 93 and 184 keV or 93, 184, and 296 keV. Maximum energy of positron emission is at 1.9 MeV.