Clinical applications of Gallium-68

Abstract

Gallium-68 is a positron-emitting radioisotope that is produced from a (68)Ge/(68)Ga generator. As such it is conveniently used, decoupling radiopharmacies from the need for a cyclotron on site. Gallium-68-labeled peptides have been recognized as a new class of radiopharmaceuticals showing fast target localization and blood clearance. (68)Ga-DOTATOC, (8)Ga-DOTATATE, (68)Ga-DOTANOC, are the most prominent radiopharmaceuticals currently in use for imaging and differentiating lesions of various somatostatin receptor subtypes, overexpressed in many neuroendocrine tumors. There has been a tremendous increase in the number of clinical studies with (68)Ga over the past few years around the world, including within the United States. An estimated ∼10,000 scans are being performed yearly in Europe at about 100 centers utilizing (68)Ga-labeled somatostatin analogs within clinical trials. Two academic sites within the US have also begun to undertake human studies. This review will focus on the clinical experience of selected, well-established and recently applied (68)Ga-labeled imaging agents used in nuclear medicine.

Figure 1

Selected acyclic chelating agents that are used in clinical trials as “gallium-essential” imaging agents.

Figure 2

A comparison of normal physiologic biodistribution of ⁶⁷Ga-citrate whole-body scintigraphy and ⁶⁸Ga-citrate PET/CT. Reprinted with permission from: Nanni et al. J Nucl Med 51, 1932–1936.

Fig. 3

Structures of somatostatin octapeptides (octreotride, OC) and related peptide analogs, TOC, TATE and NOC. Amino acid residues shown in blue constitute the recognition site of the somatostatin receptor (SSTR).

Figure 4

Lesions demonstrating higher uptake of ⁶⁸Ga-DOTATOC than ⁶⁸Ga-DOTATATE in the same patient. (A) From left to right: ⁶⁸Ga-DOTATOC PET maximum-intensity projection (MIP), ⁶⁸Ga- DOTATOC PET, CT, and PET/CT fusion; (B) from left to right: ⁶⁸Ga-DOTATATE PET MIP, ⁶⁸Ga-DOTATATE PET, and PET/CT fusion. Arrow in the MIP images in (A) and (B) depicts ileal carcinoid. Note higher radiopharmaceutical uptake in metastatic foci within liver on the ⁶⁸Ga-DOTATOC (A) images. Axial images are obtained at the level of the carcinoid tumor. Reprinted with permission from: Poeppel et al., J Nucl Med 2011; 52:1864 –1870.

Figure 5

Structure of the ⁶⁸Ga-bombesin analog, DOTAPEG₂-BN(6–14) amide ([68Ga]-BZH₃).

Figure 6

Structure of the DOTA-conjugated bisphosphonate, BPAMD.

Figure 7

Structure of ⁶⁸Ga-NOTA-RGD.

Figure 8

A 64-year-old woman with NET diagnosed in 2001 (liver lesions identified at routine abdominal ultrasound were interpreted as benign). The patient underwent hysterectomy and ovariectomy and metastases were found in both ovaries as well as in lymph nodes resected in the lumbar region. OctreoScan^™ showed positive liver lesions, but no primary tumor. Octreotide therapy (Sandostatin LAR^™ 20mg) was started, but progressive disease occurred in 2007. (A) Gallium-68-DOTATOC imaging at that time showed an intense SSTR-positive liver lesion in S8 (SUV_max = 33) and another, small lesion in S2 (SUV_max = 6.2), long solid and dashed arrows, respectively, on the maximum intensity projection image. The primary tumor was detected in the presacral region (SUV_max = 70.1) (short arrow). Left axial images (center column) are obtained at the level of the large liver lesion; right axial images (right column) are obtained at the level of the presacral tumor. (B) Peptide receptor radionuclide therapy (PRRT) was started in July 2007 (two cycles using a total of 8 GBq ⁹⁰Y-DOTATATE) and follow-up PET/CT in January, 2009 showed complete remission of the liver metastases and partial response of the presacral lesion. To date, the patient is alive and doing well (nearly five years after PRRT) (Courtesy: Dr Richard P. Baum).

Figure 8

A 64-year-old woman with NET diagnosed in 2001 (liver lesions identified at routine abdominal ultrasound were interpreted as benign). The patient underwent hysterectomy and ovariectomy and metastases were found in both ovaries as well as in lymph nodes resected in the lumbar region. OctreoScan^™ showed positive liver lesions, but no primary tumor. Octreotide therapy (Sandostatin LAR^™ 20mg) was started, but progressive disease occurred in 2007. (A) Gallium-68-DOTATOC imaging at that time showed an intense SSTR-positive liver lesion in S8 (SUV_max = 33) and another, small lesion in S2 (SUV_max = 6.2), long solid and dashed arrows, respectively, on the maximum intensity projection image. The primary tumor was detected in the presacral region (SUV_max = 70.1) (short arrow). Left axial images (center column) are obtained at the level of the large liver lesion; right axial images (right column) are obtained at the level of the presacral tumor. (B) Peptide receptor radionuclide therapy (PRRT) was started in July 2007 (two cycles using a total of 8 GBq ⁹⁰Y-DOTATATE) and follow-up PET/CT in January, 2009 showed complete remission of the liver metastases and partial response of the presacral lesion. To date, the patient is alive and doing well (nearly five years after PRRT) (Courtesy: Dr Richard P. Baum).