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.
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BibTeX
@article{dardel2026comparison,
title = {{Comparison between [68Ga]Ga-NODAGA-RGDyK and [18F]FET for the assessment of gliomas: results of a pilot study}},
author = {Nathalie Testart Dardel and Silvano Gnesin and Vincent Dunet and Luis Schiappacasse and Daniela Ferraro and Rita De Micheli and Monika E. Hegi and Andreas F. Hottinger and John O. Prior and Francesco Cicone},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-74657-3},
url = {https://www.nature.com/articles/s41598-026-74657-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparison between [68Ga]Ga-NODAGA-RGDyK and [18F]FET for the assessment of gliomas: results of a pilot study
AU - Nathalie Testart Dardel
AU - Silvano Gnesin
AU - Vincent Dunet
AU - Luis Schiappacasse
AU - Daniela Ferraro
AU - Rita De Micheli
AU - Monika E. Hegi
AU - Andreas F. Hottinger
AU - John O. Prior
AU - Francesco Cicone
PY - 2026
DA - 2026/10/08
JO - Scientific Reports
DO - 10.1038/s41598-026-74657-3
UR - https://www.nature.com/articles/s41598-026-74657-3
AB - 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.
SN - 2045-2322
ER -