Coming of age for gallium-68 neuroendocrine imaging

Long past are the days when fluorodeoxyglucose was the primary workhorse for imaging neuroendocrine tumors (NETs). Now there is a veritable cornucopia of agents to choose from, but a family of compounds radiolabeled with gallium-68 have been gaining a lot of headway. These are Ga-68 DOTANOC, DOTATOC and DOTATATE.

Among these, the latter two have been gaining more attention in recent studies and DOTATOC was just approved for orphan drug status in November by the FDA—exclusively for the detection of NETs. An exhaustive review of the viability of gallium-68 radiopharmaceuticals was published Dec. 10 in Theranostics, written by expert and sole author Irina Velikyan, PhD, associate professor at the PET-Centre at the Centre for Medical Imaging at Uppsala University Hospital, Uppsala, Sweden. Velikyan shared her knowledge about these agents in an exclusive interview with Molecular Imaging.

The benefits of these agents over and above F-18 fluorodeoxyglucose (F-18 FDG) and other options are in their leaning toward personalized medicine and physiology-specific imaging of NETs.

“The development of disease-specific imaging and therapeutic agents is the core of the current progress of nuclear medicine,” noted Velikyan. “The critical advantages of Ga-68 DOTATATE and Ga-68 DOTATOC are the specificity of their binding to the somatostatin receptors characteristically overexpressed in NETs, quantitative diagnostics and the possibility to select and follow up patients that might benefit from the radiotherapy using Y-90 or Lu-177 labeled somatostatin analogues, thus resulting in personalized medicine as well as simpler and cost-effective manufacturing procedure.”

Peptide imaging is what gallium-68 agents do best, according to the available literature. In addition to somatostatin receptors, these agents also have been found to point out amino-acid uptake, glucose transport and angiogenesis, all imaging pathways that could be applicable to NETs. For now, somatostatin receptor imaging is the primary focus, for a list of reasons.

“The clinical superiority of Ga-68 labeled somatostatin analogues in terms of specificity, sensitivity, staging accuracy, detection rate, quantification, acquisition time, simpler agent production and patient examination logistics as well as lower cost has already been demonstrated,” explained Velikyan.

The condition put forth by the FDA for the approval of orphan drug status was clinical evidence of its superiority over the conventional standard, I-111 pentetreotide. This appears to not be a problem as evidence suggests that Ga-68 imaging of NETs may be more powerful than pentetreotide.

“Ga-68/PET-CT using somatostatin analogues is becoming a new golden standard in imaging of NETs with specificity and sensitivity well above 90 percent and advantages over conventional radiologic and scintigraphic imaging, replacing I-111-pentetreotide (Octreoscan),” Velikyan remarked.

Further study will prove which of the three will take a definitive lead in clinical use, but at least one, if not more, appears to have something of a red carpet rolled out for future standard practice.