RT Journal Article
SR Electronic
T1 Prospective Phase II Trial of [<sup>68</sup>Ga]Ga-NODAGA-E[c(RGDyK)]<sub>2</sub> PET/CT Imaging of Integrin α<sub>v</sub>β<sub>3</sub> for Prognostication in Patients with Neuroendocrine Neoplasms
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 252
OP 259
DO 10.2967/jnumed.122.264383
VO 64
IS 2
A1 Esben Andreas Carlsen
A1 Mathias Loft
A1 Annika Loft
A1 Dorota Czyzewska
A1 Mikkel Andreassen
A1 Seppo W. Langer
A1 Ulrich Knigge
A1 Andreas Kjaer
YR 2023
UL http://jnm.snmjournals.org/content/64/2/252.abstract
AB Integrin αvβ3, a subtype of the arginine-glycine-aspartate (RGD)–recognizing cell surface integrins, is upregulated on endothelial cells during angiogenesis and on tumor cells. Because of involvement in tumor growth, invasiveness and metastases, and angiogenesis, integrin αvβ3 is an attractive target in cancers. In this study, we applied 68Ga-NODAGA-E[c(RGDyK)]2 for imaging of integrin αvβ3 in patients with neuroendocrine neoplasms (NENs) and its potential use for prognostication. We hypothesized that 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT would show tumor lesion uptake and that higher tumor lesion uptake was associated with a poorer prognosis. Methods: Between December 2017 and November 2020 we prospectively enrolled 113 patients with NEN of all grades (2019 World Health Organization classification) for 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT. The scan was acquired 45 min after injection of 200 MBq of 68Ga-NODAGA-E[c(RGDyK)]2. Board-certified specialists in nuclear medicine and radiology analyzed the PET/CT measuring SUVmax in tumor lesions. Positive tumor lesions were defined as those with tumor-to-liver background ≥ 2. Maximal tumor SUVmax for each patient was used as a predictor of outcome. Patients were followed for at least 1 y to assess progression-free survival and overall survival. Results: Of 113 patients enrolled in the trial, 99 underwent 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT, with 97 patients having evaluable lesions. The patients predominantly had small intestinal (64%) or pancreatic (20%) NEN and most had metastatic disease (93%). Most patients had low-grade tumors (78%), whereas 22% had high-grade tumors. During a median follow-up of 31 mo (interquartile range, 26–38 mo), 62 patients (64%) experienced disease progression and 25 (26%) patients died. In total, 76% of patients had positive tumor lesions, and of the patients with high-grade tumors 91% had positive tumor lesions. High integrin αvβ3 expression, defined as an SUVmax of at least 5.25, had a hazard ratio of 2.11 (95% CI, 1.18–3.78) and 6.95 (95% CI, 1.64–29.51) for progression-free survival and overall survival, respectively (P = 0.01 for both). Conclusion: Tumor lesion uptake of 68Ga-NODAGA-E[c(RGDyK)]2 was evident in patients with all grades of NEN. High uptake was associated with a poorer prognosis. Further studies are warranted to establish whether 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT may become a prediction tool for identification of patients eligible for treatments targeting integrin αvβ3.