Back To Search Results

Gallium Scan

Editor: Orlando De Jesus Updated: 12/26/2022 11:35:05 PM

Introduction

A gallium scan is a study that uses intravenously injectable isotopes of gallium to produce nuclear medicine images. Gallium was 1 of the first radioisotopes used for diagnostic nuclear medicine. Gallium, discovered in 1875 by Paul-Émile Lecoq de Boisbaudran, was first considered for diagnostic and therapeutic medical use in the 1940s by the research of H. C. Dudley and his co-workers. Gallium scans were initially used for localizing tumors and abscesses. Commercially available radiopharmaceuticals gallium-67 (67Ga) and gallium-68 (68Ga) are widely used. Although gallium-72 proved less useful for medical use, gallium-67, produced by proton-bombarded zinc, and particularly gallium-68, produced by generator accelerating of germanium-68 (68Ge), emerged as solid contenders after measurement instrumentation became more advanced. Initially, gallium-67 was unexpectedly found to highlight Hodgkin’s lymphoma, although it was intended for osseous cancer. It was later realized that the isotope could be used for a broader range of malignancies and inflammatory processes.[1] Historically, gallium-67 scans were used to diagnose many diseases, including bone infections, cancers (especially lymphomas), fevers of unknown origin, non-specific inflammation, and intra-abdominal abscesses. It was also used to evaluate inflammatory diseases of the lungs, like sarcoidosis, interstitial pneumonitis, pulmonary tuberculosis, and pulmonary fibrosis.[2] Gallium-67 is used with single-photon emission computed tomography (SPECT), while gallium-68 is used with positron emission tomography (PET).

Gallium is a trivalent metal treated similarly to the body's ferric iron. Gallium-67 is relatively insoluble at normal pH and requires substances like citrate ions to form a complex to dissolve once in the body. Roughly 75% of the administered dose remains in the body after 48-72 hours and distributes evenly in soft tissues, liver, and bone. Around 90% of 67Ga is bound to transferrin in the blood plasma. Subsequently, it dissociates at low pH (exudate or tumor site) and binds to lactoferrin due to increased vascular flow in the area. White blood cells may bind and transport 67Ga as well. Siderophores produced by bacteria have a good affinity for 67Ga and can form a complex to be taken up by the bacteria. It is also thought that bacteria directly uptake 67Ga via facilitated diffusion and nonspecific binding sites.[3] 

Gallium-68 (68Ga) is a positron-emitting isotope with a half-life of 68 minutes. It can be generated from germanium-68 or zinc-68. It can be used for the inherent properties in the radiometal itself or the chelated agent's chemical properties (most commonly a somatostatin analog). It is often attached to a specific chelating agent to be used as a tracer (eg, DOTA-octreotate, also known as DOTATATE). The agent keeps gallium stably bound and free to distribute while binding to a specific receptor molecule. DOTATATE, DOTATOC, and DOTANOC are also referred to as GaTate, GaToc, and GaNoc, respectively. Bifunctional chelating binds the metal (68Ga3+ ion) to a complex. The complex should have a high affinity with gallium for in vivo stability. In contrast, the targeting biomolecule (ex., drug, peptide, or antibody) in the complex can bind to a specific site and concentrate there. Essentially, gallium is paired with a compound that binds to a target tissue site. The complex is injected intravenously and is imaged with a PET detector at specific times depending on the desired target site uptake, but usually after 1 hour. In the case of GaTate, affinity is highest to the somatostatin receptor (SSTR) subtype 2. This leads to intense uptake in the spleen, adrenal glands, kidneys (not due to SSTR), and pituitary, with moderate intensity in the liver (not due to SSTR), thyroid, and saliva glands. There is also uptake in other areas, such as the pancreas, bone, brain, and lymph nodes.[4] GaToc has a high affinity to SSTR subtype 5, and GaNoc has a high affinity to SSTR subtypes 3 and 5. A homogenous uptake is physiologic, while intense heterogeneous, irregular focal uptake is worrying. The PET scan is usually done with a whole-body computed tomography (CT) scan for detailed anatomical mapping, referred to as a PET/CT scan.

The renewed interest in gallium is due to its widespread availability as it is generator-produced and has a short half-life. Using gallium, on-site labeling, and radiopharmaceutical use can be done without a cyclotron nearby or delivering the product. The radiolabel pair has varying sensitivity and specificity inherent to the tissue or receptor properties.[5] DOTATATE has recently been given orphan drug status, which has also renewed some interest in gallium-68.

Gallium-67 is a gamma-emitting isotope with a half-life of 3.26 days that was used for imaging many pathologies, although now, fluorine-18 (18F) fluoro-deoxyglucose (FDG) (18F-FDG) has mostly replaced it. Both isotopes require a high-energy cyclotron for production and for doses to be individually purchased; therefore, they are not always available. 18F-FDG, a nonspecific metabolic indicator using glucose metabolism, has mostly replaced gallium-67, but recently, there have been new developments in gallium’s utility, now as a gallium-68 labeled radiotracer. This evolution includes a shorter half-life, on-site generation, somatostatin receptor, prostate (68Ga-PSMA-11 PET/MR) tracers, and other cancer diagnoses, including bony and soft tissue metastasis.[6][7] Gallium-67 (67Ga) is still used for imaging inflammation and granulomatous reactions. It produces low resolution and image quality and has a high radiation burden to patients due to its longer half-life. Imaging takes place at least 2 days after injection due to this long half-life. Gallium-67 is commonly bonded with citrate or nitrate (both dissociate in the blood when injected, leaving the gallium ion, 67Ga3+). Although WBC SPECT imaging has mostly replaced gallium-67 for infection imaging, there are still specific circumstances for it to be used. Examples include ruling out false negatives in spinal infections, immunocompromised patients, and chronic infections.[8]

Gallium-68 is typically created by a 68Ge/68Ga generator. This process has an advantage over 18F-FDG, as 68Ga does not require a nearby cyclotron, and the parent isotope 68Ge has a half-life of 271 days. 68Ge is usually made from proton bombardment of 69Ga.[9] 68Ge decays through electron capture. 68Ga mostly decays through positron emission (yields 89%) with a mean MeV of 0.89 and maximum energy of 1.9MeV.[10] That is higher energy than 18F (with positron yield 96.7%), 0.25 MeV and max 0.63MeV. Since lower positron emission yields and higher endpoint energy emission lead to lower resolution in PET scans, Gallium has a theoretically lower resolution in imaging. Gallium has lower sensitivity and inferior spatial resolution than 18F, but gallium has a high clinical image contrast when labeled, making lesion detection easier.[10] Moreover, both radionuclides produce high-quality imaging as long as a 3mm detection scanner is used.[11] Imaging can occur in approximately 1 hour due to the short half-life. The 68Ga3+ cation allows it to join various molecules using oxygen, nitrogen, and sulfur as atom donors. Due to increased gallium-68 demands, it can also be created by a medical cyclotron.[12] Originally, 68Ga was paired with ligands such as EDTA (ethylenediaminetetraacetic acid) derivatives, and years later, developed pairing with DTPA (diethylenetriaminepentaacetic acid) or DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based derivatives. This allowed 68Ga-DOTA-octreotate to become an alternative to Indium-111-DTPA-octreoscan.[13] 68Ga can be paired with many molecules, including citrate, which gives it the same site affinities as 67Ga but a lower half-life. There are currently trials pairing 68Ga with antimicrobials such as ciprofloxacin and DOTA-depsidomycin.[8]

Procedures

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Procedures

Before the procedure begins, the medical team reviews the patient's critical medical information. The patient is informed in detail of the procedure, and with the agreement, the study begins. Food and liquid restrictions are not required, but the patient should be well-hydrated and have regular bowel movements. The kidneys eliminate the 68Ga-DOTA-conjugates, while the kidneys and bowel eliminate the 67Ga-citrate.

The radiopharmaceutical agent is delivered intravenously to the patient with no interacting substances. The activity administered should be above 100MBq, but it can range from 100-200MBq. For example, 67Ga should be 185MBq, 5mCi in adults, and 3.7-7.4MBq/kg, 0.1 to 0.2mCi/kg in children.[14] The time before scanning depends on the compound used. Usually, between 45 minutes to 90 minutes for 68Ga bound compounds varies depending on the desired target organ uptake and the compound used. Images for 67Ga are taken 48 hours after administration, then 72 hours for delayed images, and even up to 5 days after to help differentiate lesions.

The patient should void their bladder before scanning to remove unbound radioactive compounds and reduce image noise, allowing better imaging of the area and decreasing radiation exposure to the urinary tract. Metals on the body are also removed during the procedure due to their potential for imaging interference. The patient's whole body is imaged with typical imaging times of approximately 30 to 60 minutes per view, but it depends on the size. The patient should remain still and quiet during imaging to reduce motion artifacts. The patient is discharged after the scan is completed when the radiation emission levels are safe and reviewed by the physician.

The patient should avoid contact with pregnant women and infants for as long as the physician advises. A waiting period of 7 half-lives allows less than 1% of original radiation to persist. This guide can also be used as a general safety rule during breastfeeding. The nuclear radiologist uses the patient's acquired relevant history to report the image in detail.

Indications

Neuroendocrine tumors (68Ga-DOTA-TATE, DOTA-NOC, DOTA-TOC): 68Ga conjugates should be used as the preferred functional imaging modality for the evaluation of neuroendocrine tumors (NETs) for all histological grades.[15][16] Ideally, it is used alone for histological well-differentiated/low-grade tumors; however, if the tumor is not well-differentiated, it should be used with the 18F-FDG PET/CT scan.[16][17][18][19][20] NETs include pituitary adenoma, pancreatic islet cell tumors, carcinoid, pheochromocytoma, paraganglioma, medullary thyroid cancer, and small cell lung carcinoma.[5]

Prostate cancer: (68Ga-labeled inhibitors of prostate-specific membrane antigen (68Ga-PSMA), 68Ga-bombesin/68Ga-RM2, 68Ga-DOTATOC) [17][20][21]

67Ga-citrate is mainly used for lymphomas (Hodgkin’s and non-Hodgkin’s) and fever of unknown origin. Although more effective agents exist, they can still be used for lung cancer, lung inflammatory diseases, bone infections, melanoma, germ cell tumors, hepatocellular carcinoma, neuroblastoma, multiple myeloma, sarcoma, and head and neck tumors. 67Ga is only used for spinal infections when FDG cannot be performed.[22]

Emerging indications for 68Ga:

  • 68Ga-DOTATATE may play a role in other somatostatin receptor tumors such as renal cell cancer, breast cancer, prostate cancer, malignant lymphoma, hepatocellular cancer, medulloblastoma, neuroblastoma, sarcoma, and gastric cancer.[23][24]
  • Meningioma (68-DOTATATE) [17][24][25]
  • Osteomyelitis and discitis (68Ga-citrate) [26][27]
  • Breast cancer (68Ga-bombesin, 68Ga-ABY-002) [28]
  • Melanoma (68Ga-melanocortin) [29][30]
  • Tumor therapy response (68Ga binding to DOTA-related analogs such as P-glycoprotein, cholecystokinin, neurotensin, and substance P) [17]
  • Pathologic angiogenic processes (68Ga-RGB, arginine, glycine, aspartic acid peptides) [17]
  • Alzheimer’s disease (68Ga-DOTA-C3-BF) [31]
  • Cerebral amyloid angiopathy [32]
  • Pathology with activated macrophages (68Ga-deferoxamine-folate). Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, diabetes, vasculitis, sarcoidosis, and atherosclerosis.[33]
  • Cardiac imaging (68Ga-NOTA/DOTA-RGD, 68Ga-DOTAVAP-PEG-P). Myocarditis, atherosclerotic plaques, and post-myocardial infarction inflammation [17]
  • Respiratory imaging (68Ga-DOTA-NOC) in pulmonary fibrosis and (68Ga-DOTATATE) in sarcoidosis [8][17]
  • Inflammatory bowel disease (68Ga-Citrate) [8]
  • Colorectal, esophagus, breast, lung, pancreatic, head, and neck cancers (68Ga-fibroblast-activation-protein inhibitors) (68Ga-FAPI) [34]
  • Pulmonary embolism (68Ga-carbon nanoparticles and 68Ga-macro-aggregated albumin) [35][36]

Interfering Factors

Blood transfusions and hemolysis can interfere with the body's iron distribution; thus, it is not recommended to have a gallium-citrate scan after a recent transfusion due to uptake anomalies. Depending on the conjugated molecule for 68Ga scans, metabolic interference from various substances could occur. For example, therapeutic somatostatin analogs may interfere with 68Ga-DOTATATE scans, so if possible, short-acting somatostatin analogs should be stopped 24 hours before the scan.

Motion artifacts may be a source of error. Other sources of error include but are not limited to misinterpreting physiological uptake areas, anatomical uptake variation, clothing and skin contamination with urine, recent procedures or trauma, recent or current chemotherapy, medication-related uptake changes (ex. somatostatin analogs decreasing uptake of 68Ga-DOTATATE, or granulocyte-colony stimulating factor increasing bone uptake of gallium), and rarely instrumentation calibration error (eg, PET/CT superimposition error).[25]

Complications

Some rare allergic reactions can occur and include but are not limited to erythema, rash, pruritis, nausea, vomiting, tachycardia, dizziness, and syncope.[37][38]

There are no contraindications to the gallium scan, but precautions should be taken to avoid complications:

  • Whether suspected or confirmed, a clinical decision of risks versus benefits must be made during pregnancy.
  • Breastfeeding should be discontinued, with milk extraction post-procedure, and resumed when the radiation dose to the child is less than 1mSv. It is recommended to wait 8 hours after the 68Ga scan before milk extraction, and breastfeeding should resume.
  • Pediatric cases should be carefully evaluated to avoid radiation exposure unless there is a clear suspicion of malignancy.
  • It may be beneficial to cease somatostatin analog therapy before a DOTA scan.

Patient Safety and Education

Radioactive gallium isotopes are inherently hazardous to one's health. Both healthcare staff and patients must be aware of the dangers and take reasonable precautions. The patient should be informed that the risk of radiation exposure is less than the scan's benefits and should understand why the scan is indicated. They should also understand others' risks when they emit radiation, especially to children, during lactation and pregnancy. The patient should be encouraged to ask questions about safety concerns.

Organs have different uptake of the isotope, and there are individual variations as well. For example, a patient post-splenectomy would have higher uptake in other organs. The average effective whole-body dose of 67Ga is 18.5mSv, while 68Ga-DOTATATE is 3.0mSv.[39][40] With a comparatively significant reduction in effective dose, 68Ga is starting to have lower exposure to adverse outcomes.[41]

Clinical Significance

Until recently, gallium scans could detect many pathologies, but they have been phased out due to newer developments (eg, 18F-FDG). Gallium was limited to detecting cancer and inflammatory processes only, but now the gallium redux is expanding to detect all kinds of pathology with gallium-68 as a radiotracer. Gallium scans are adjuncts for diagnosis, although some conjugates have specific receptors. Gallium is distributed in the body according to the conjugate used. If citrate is used, gallium's natural properties allow the body to metabolize it like ferric iron.

If gallium is chelated with other molecules (eg, DOTATATE), it distributes in the body according to the receptor's affinity for that molecule. An abnormal accumulation of gallium implies a localization of underlying pathology, either tumor or inflammation with citrate as a conjugate or specific pathologies (eg, NETs), depending on the conjugate molecule.

68Ga can be conjugated with various molecules to help diagnose multiple pathologies. It is primarily used for cancer detection (NETs and prostate cancer). It can detect stage, post-treatment response, and cancer surveillance. It can be used alone but is usually complementary to other imaging methods (ex. 18F-FDG PET, CT, MRI, etc.) for more detailed anatomy and specificity. Further developments and research may allow gallium-68 scans to adequately diagnose pulmonary embolisms, cardiac pathologies, respiratory pathologies, Alzheimer's disease, bone infections, and other cancers.

67Ga-citrate is primarily used to help diagnose lymphomas (Hodgkin's and non-Hodgkin's, especially for restaging) and fevers of unknown origin. It may also be used in certain cancers (eg, bronchogenic carcinoma), although 18F-FDG has superseded it.

References


[1]

Hayes RL. The medical use of gallium radionuclides: a brief history with some comments. Seminars in nuclear medicine. 1978 Jul:8(3):183-91     [PubMed PMID: 362533]

Level 3 (low-level) evidence

[2]

Forgacs P. The gallium scan and inflammatory lesions. Archives of internal medicine. 1982 Feb:142(2):231     [PubMed PMID: 7059247]


[3]

Goldsmith SJ, Vallabhajosula S. Clinically proven radiopharmaceuticals for infection imaging: mechanisms and applications. Seminars in nuclear medicine. 2009 Jan:39(1):2-10. doi: 10.1053/j.semnuclmed.2008.08.002. Epub     [PubMed PMID: 19038596]

Level 3 (low-level) evidence

[4]

Kuyumcu S, Özkan ZG, Sanli Y, Yilmaz E, Mudun A, Adalet I, Unal S. Physiological and tumoral uptake of (68)Ga-DOTATATE: standardized uptake values and challenges in interpretation. Annals of nuclear medicine. 2013 Jul:27(6):538-45. doi: 10.1007/s12149-013-0718-4. Epub 2013 Mar 31     [PubMed PMID: 23543506]


[5]

Banerjee SR, Pomper MG. Clinical applications of Gallium-68. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. 2013 Jun:76():2-13. doi: 10.1016/j.apradiso.2013.01.039. Epub 2013 Feb 20     [PubMed PMID: 23522791]


[6]

Park SY, Zacharias C, Harrison C, Fan RE, Kunder C, Hatami N, Giesel F, Ghanouni P, Daniel B, Loening AM, Sonn GA, Iagaru A. Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer. Radiology. 2018 Aug:288(2):495-505. doi: 10.1148/radiol.2018172232. Epub 2018 May 22     [PubMed PMID: 29786490]


[7]

Pianou NK, Stavrou PZ, Vlontzou E, Rondogianni P, Exarhos DN, Datseris IE. More advantages in detecting bone and soft tissue metastases from prostate cancer using (18)F-PSMA PET/CT. Hellenic journal of nuclear medicine. 2019 Jan-Apr:22(1):6-9. doi: 10.1967/s002449910952. Epub 2019 Mar 7     [PubMed PMID: 30843003]


[8]

Vorster M, Maes A, Wiele Cv, Sathekge M. Gallium-68 PET: A Powerful Generator-based Alternative to Infection and Inflammation Imaging. Seminars in nuclear medicine. 2016 Sep:46(5):436-47. doi: 10.1053/j.semnuclmed.2016.04.005. Epub     [PubMed PMID: 27553469]


[9]

Kumar K. The Current Status of the Production and Supply of Gallium-68. Cancer biotherapy & radiopharmaceuticals. 2020 Apr:35(3):163-166. doi: 10.1089/cbr.2019.3301. Epub 2020 Mar 20     [PubMed PMID: 32196363]


[10]

Sanchez-Crespo A. Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. 2013 Jun:76():55-62. doi: 10.1016/j.apradiso.2012.06.034. Epub 2012 Aug 29     [PubMed PMID: 23063597]

Level 3 (low-level) evidence

[11]

Velikyan I. Positron emitting [68Ga]Ga-based imaging agents: chemistry and diversity. Medicinal chemistry (Shariqah (United Arab Emirates)). 2011 Sep:7(5):345-79     [PubMed PMID: 21711223]

Level 3 (low-level) evidence

[12]

Riga S,Cicoria G,Pancaldi D,Zagni F,Vichi S,Dassenno M,Mora L,Lodi F,Morigi MP,Marengo M, Production of Ga-68 with a General Electric PETtrace cyclotron by liquid target. Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB). 2018 Nov;     [PubMed PMID: 30473059]


[13]

Martiniova L, Palatis L, Etchebehere E, Ravizzini G. Gallium-68 in Medical Imaging. Current radiopharmaceuticals. 2016:9(3):187-207. doi: 10.2174/1874471009666161028150654. Epub     [PubMed PMID: 27804868]


[14]

Bombardieri E, Aktolun C, Baum RP, Bishof-Delaloye A, Buscombe J, Chatal JF, Maffioli L, Moncayo R, Mortelmans L, Reske SN. 67Ga scintigraphy: procedure guidelines for tumour imaging. European journal of nuclear medicine and molecular imaging. 2003 Dec:30(12):BP125-31     [PubMed PMID: 14989225]

Level 1 (high-level) evidence

[15]

Andreasi V, Partelli S, Muffatti F, Manzoni MF, Capurso G, Falconi M. Update on gastroenteropancreatic neuroendocrine tumors. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2021 Feb:53(2):171-182. doi: 10.1016/j.dld.2020.08.031. Epub 2020 Sep 8     [PubMed PMID: 32912771]


[16]

You H, Kandathil A, Beg M, De Blanche L, Kazmi S, Subramaniam RM. Ga-68 DOTATATE PET/CT and F-18 FDG PET/CT in the evaluation of low and intermediate versus high-grade neuroendocrine tumors. Nuclear medicine communications. 2020 Oct:41(10):1060-1065. doi: 10.1097/MNM.0000000000001255. Epub     [PubMed PMID: 32732600]


[17]

Khan MU, Khan S, El-Refaie S, Win Z, Rubello D, Al-Nahhas A. Clinical indications for Gallium-68 positron emission tomography imaging. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2009 Jun:35(6):561-7. doi: 10.1016/j.ejso.2009.01.007. Epub 2009 Feb 7     [PubMed PMID: 19201567]


[18]

Chauhan A, El-Khouli R, Waits T, Agrawal R, Siddiqui F, Tarter Z, Horn M, Weiss H, Oates E, Evers BM, Anthony L. Post FDA approval analysis of 200 gallium-68 DOTATATE imaging: A retrospective analysis in neuroendocrine tumor patients. Oncotarget. 2020 Aug 11:11(32):3061-3068. doi: 10.18632/oncotarget.27695. Epub 2020 Aug 11     [PubMed PMID: 32850010]

Level 2 (mid-level) evidence

[19]

Panagiotidis E, Alshammari A, Michopoulou S, Skoura E, Naik K, Maragkoudakis E, Mohmaduvesh M, Al-Harbi M, Belda M, Caplin ME, Toumpanakis C, Bomanji J. Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Jan:58(1):91-96. doi: 10.2967/jnumed.116.178095. Epub 2016 Aug 11     [PubMed PMID: 27516446]


[20]

Kayani I, Conry BG, Groves AM, Win T, Dickson J, Caplin M, Bomanji JB. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2009 Dec:50(12):1927-32. doi: 10.2967/jnumed.109.066639. Epub 2009 Nov 12     [PubMed PMID: 19910422]

Level 2 (mid-level) evidence

[21]

Sasikumar A. Specificity of (68)Ga-PSMA PET/CT for Prostate Cancer - Myths and Reality. Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India. 2017 Jan-Mar:32(1):11-12. doi: 10.4103/0972-3919.198449. Epub     [PubMed PMID: 28242976]


[22]

Love C, Palestro CJ. Nuclear medicine imaging of bone infections. Clinical radiology. 2016 Jul:71(7):632-46. doi: 10.1016/j.crad.2016.01.003. Epub 2016 Feb 17     [PubMed PMID: 26897336]


[23]

Reubi JC, Waser B, Schaer JC, Laissue JA. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. European journal of nuclear medicine. 2001 Jul:28(7):836-46     [PubMed PMID: 11504080]


[24]

van der Lely AJ, de Herder WW, Krenning EP, Kwekkeboom DJ. Octreoscan radioreceptor imaging. Endocrine. 2003 Apr:20(3):307-11     [PubMed PMID: 12721512]


[25]

Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, Ambrosini V, Kjaer A, Delgado-Bolton R, Kunikowska J, Oyen WJG, Chiti A, Giammarile F, Sundin A, Fanti S. Guideline for PET/CT imaging of neuroendocrine neoplasms with (68)Ga-DOTA-conjugated somatostatin receptor targeting peptides and (18)F-DOPA. European journal of nuclear medicine and molecular imaging. 2017 Aug:44(9):1588-1601. doi: 10.1007/s00259-017-3728-y. Epub 2017 May 25     [PubMed PMID: 28547177]


[26]

Nanni C,Errani C,Boriani L,Fantini L,Ambrosini V,Boschi S,Rubello D,Pettinato C,Mercuri M,Gasbarrini A,Fanti S, 68Ga-citrate PET/CT for evaluating patients with infections of the bone: preliminary results. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2010 Dec;     [PubMed PMID: 21078801]


[27]

Vorster M, Maes A, Van deWiele C, Sathekge M. Gallium-68: a systematic review of its nononcological applications. Nuclear medicine communications. 2013 Sep:34(9):834-54. doi: 10.1097/MNM.0b013e32836341e5. Epub     [PubMed PMID: 23812409]

Level 3 (low-level) evidence

[28]

Tolmachev V, Velikyan I, Sandström M, Orlova A. A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue. European journal of nuclear medicine and molecular imaging. 2010 Jul:37(7):1356-67. doi: 10.1007/s00259-009-1367-7. Epub 2010 Feb 4     [PubMed PMID: 20130858]

Level 3 (low-level) evidence

[29]

Yang J, Xu J, Gonzalez R, Lindner T, Kratochwil C, Miao Y. (68)Ga-DOTA-GGNle-CycMSH(hex) targets the melanocortin-1 receptor for melanoma imaging. Science translational medicine. 2018 Nov 7:10(466):. doi: 10.1126/scitranslmed.aau4445. Epub     [PubMed PMID: 30404861]


[30]

Froidevaux S, Calame-Christe M, Schuhmacher J, Tanner H, Saffrich R, Henze M, Eberle AN. A gallium-labeled DOTA-alpha-melanocyte- stimulating hormone analog for PET imaging of melanoma metastases. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2004 Jan:45(1):116-23     [PubMed PMID: 14734683]

Level 3 (low-level) evidence

[31]

Asti M, Ferrari E, Croci S, Atti G, Rubagotti S, Iori M, Capponi PC, Zerbini A, Saladini M, Versari A. Synthesis and characterization of (68)Ga-labeled curcumin and curcuminoid complexes as potential radiotracers for imaging of cancer and Alzheimer's disease. Inorganic chemistry. 2014 May 19:53(10):4922-33. doi: 10.1021/ic403113z. Epub 2014 Apr 25     [PubMed PMID: 24766626]


[32]

Zha Z, Song J, Choi SR, Wu Z, Ploessl K, Smith M, Kung H. (68)Ga-Bivalent Polypegylated Styrylpyridine Conjugates for Imaging Aβ Plaques in Cerebral Amyloid Angiopathy. Bioconjugate chemistry. 2016 May 18:27(5):1314-23. doi: 10.1021/acs.bioconjchem.6b00127. Epub 2016 Apr 20     [PubMed PMID: 27045547]


[33]

Johanna Haukkala, Iina Laitinen, Pauliina Luoto, Peter Iveson, Ian Wilson, Hege Karlsen, Alan Cuthbertson, Jukka Laine, Pia Leppänen, Ylä-Herttula S, Knuuti J, Roivainen A. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice. European journal of nuclear medicine and molecular imaging. 2009 Dec:36(12):2058-67. doi: 10.1007/s00259-009-1220-z. Epub     [PubMed PMID: 19629477]

Level 3 (low-level) evidence

[34]

Vaz SC, Oliveira F, Herrmann K, Veit-Haibach P. Nuclear medicine and molecular imaging advances in the 21st century. The British journal of radiology. 2020 Jun:93(1110):20200095. doi: 10.1259/bjr.20200095. Epub 2020 May 13     [PubMed PMID: 32401541]

Level 3 (low-level) evidence

[35]

Hofman MS, Beauregard JM, Barber TW, Neels OC, Eu P, Hicks RJ. 68Ga PET/CT ventilation-perfusion imaging for pulmonary embolism: a pilot study with comparison to conventional scintigraphy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2011 Oct:52(10):1513-9. doi: 10.2967/jnumed.111.093344. Epub 2011 Sep 9     [PubMed PMID: 21908388]

Level 3 (low-level) evidence

[36]

Le Roux PY, Hicks RJ, Siva S, Hofman MS. PET/CT Lung Ventilation and Perfusion Scanning using Galligas and Gallium-68-MAA. Seminars in nuclear medicine. 2019 Jan:49(1):71-81. doi: 10.1053/j.semnuclmed.2018.10.013. Epub 2018 Nov 17     [PubMed PMID: 30545520]


[37]

Commandeur C, Richard M, Renzi PM. Severe hypersensitivity reaction to injectable Gallium 67 in a worker exposed to silica. Allergy. 1992 Aug:47(4 Pt 1):337-9     [PubMed PMID: 1332528]

Level 3 (low-level) evidence

[38]

The anterior crossbite., Weinberg RL,, Quintessence international, dental digest, 1977 Aug     [PubMed PMID: 8543992]


[39]

Keijsers RG, van den Heuvel DA, Grutters JC. Imaging the inflammatory activity of sarcoidosis. The European respiratory journal. 2013 Mar:41(3):743-51. doi: 10.1183/09031936.00088612. Epub 2012 Sep 27     [PubMed PMID: 23018903]


[40]

Josefsson A, Hobbs RF, Ranka S, Schwarz BC, Plyku D, Willegaignon de Amorim de Carvalho J, Buchpiguel CA, Sapienza MT, Bolch WE, Sgouros G. Comparative Dosimetry for (68)Ga-DOTATATE: Impact of Using Updated ICRP Phantoms, S Values, and Tissue-Weighting Factors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018 Aug:59(8):1281-1288. doi: 10.2967/jnumed.117.203893. Epub 2018 Feb 9     [PubMed PMID: 29439017]

Level 2 (mid-level) evidence

[41]

Walker RC, Smith GT, Liu E, Moore B, Clanton J, Stabin M. Measured human dosimetry of 68Ga-DOTATATE. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2013 Jun:54(6):855-60. doi: 10.2967/jnumed.112.114165. Epub 2013 Mar 20     [PubMed PMID: 23516312]