Comparison between [68Ga]Ga-NODAGA-RGDyK and [18F]FET for the assessment of gliomas: results of a pilot study

Abstract Arg-Gly-Asp peptide (RGD) binds to α v β 3 integrins, which are involved in the development of new vessels, necessary for tumor growth. Several RGD-based PET radiopharmaceuticals have been developed to visualize integrin α v β 3 expression. Differences between O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ([ 18 F]FET) and integrin-targeting radiopharmaceuticals in patients with brain tumors have not been evaluated so far. Our aim was to compare the diagnostic information provided by the α v β 3 integrin-targeting [ 68 Ga]Ga-NODAGA-RGDyK ([ 68 Ga]Ga-RGD) with that of [ 18 F]FET and contrast-enhanced T1-weighted sequences (CE-T1w) in 10 patients with newly diagnosed or recurrent diffuse glioma. After image registration, tumor segmentation of [ 68 Ga]Ga-RGD and [ 18 F]FET PET images was performed using the average background signal multiplied by 1.6 as a threshold for positivity. The contrast-enhancing tumor portions were manually delineated on CE-T1w sequences. Tumor volumes (TV) identified by all three modalities (i.e. TV RGD , TV FET , TV CE−T1w ) were compared and their spatial congruence (SC) calculated. Thirteen brain lesions from 10 patients ( n = 4 with high-grade gliomas and n = 6 with low-grade gliomas) were analyzed, all showing increased [ 18 F]FET uptake. Nine lesions were [ 68 Ga]Ga-RGD-positive, 4 were [ 68 Ga]Ga-RGD-negative, all corresponding to non-contrast enhancing lesions. Tumor-to-background ratios (TBR) were higher for [ 68 Ga]Ga-RGD-positive than for [ 18 F]FET -positive disease (median TBR = 3.92 vs. 2.12, respectively, p = 0.008). All [ 18 F]FET - and [ 68 Ga]Ga-RGD-positive lesions extended beyond the contrast-enhancing tumor portions. In the whole cohort, TV FET exceeded TV RGD (median values = 11.2 vs. 7.7 mL, p = 0.014). In most high-grade glioma lesions (i.e. 5/7), however, TV RGD was larger than TV FET . Overall, median overlapping volume between [ 68 Ga]Ga-RGD and [ 18 F]FET was 3.6 mL (range 0.1–8.13mL), and the median SC was 24.3% (range, 0.9–59.8%). [ 18 F]FET and [ 68 Ga]Ga-RGD PET provide different information. In the overall cohort, TV FET was larger than TV RGD , however TV RGD tended to be larger than TV FET in the subgroup of patients with high-grade glioma. [ 68 Ga]Ga-RGD PET may delineate regions of active neoangiogenesis extending beyond gadolinium enhancement. Trial registration : https://www.clinicaltrials.gov/study/NCT02666547 , registered 2012-08-12.