We conducted the first-in-human study of 18 F-fluoroethyl triazole [Tyr 3 ] octreotate ( 18 F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18 F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18 F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18 F-FET-βAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.
For the ABCB1 gene, G2677T/A allele frequencies were found to be similar to those reported in the literature. There was no association of G2677T/A or C3435T with clinical phenotype, or resistance to treatment. However, 77.3% of 22/222 patients who did not respond to therapy and required surgery, where found to carry both the C3434T and the G2677T mutation. Conclusion Our study was conducted in a genetically homogenous population in the island of Crete. No correlation of any single SNP was found with either clinical activity or response to treatment. However, most patients who carried both the G2677T and C3435T mutations were refractory to treatment, a finding which implies that resistance to treatment in IBD patients is a more complex issue, which requires the presence of a genetic locus rather than a single SNP.
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