Screening of JAK2 V617F and MPL W515 K/L negative essential thrombocythaemia patients for mutations in SESN2, DNAJC17, ST13, TOP1MT, and NTRK1

摘要

Purpose: Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1-5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr3-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of 68Ga-DOTA-iodo-Tyr3- octreotate [68Ga-DOTA,3-iodo-Tyr3,Thr8] octreotide (68Ga-HA-DOTATATE; HA, high-affinity) compared to the established 68Ga-DOTA-Tyr3-octreotate ( 68Ga-DOTATATE) in vivo. Methods: The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both 68Ga-HA-DOTATATE and 68Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner. Results: 68Ga-HA- DOTATATE and 68Ga-DOTATATE showed comparable uptake in the liver (SUVmean 8.9±2.2 vs. 9.3±2.5, n.s.), renal cortex (SUVmean 13.3±3.9 vs. 14.5±3.7, n.s.) and spleen (SUVmean 24.0±6.7 vs. 22.9±7.3, n.s.). A somewhat higher pituitary uptake was found with 68Ga-HA-DOTATATE (SUV mean 6.3±1.8 vs. 5.4±2.1, p0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. 68Ga-HA-DOTATATE demonstrated 328 lesions (95.3 % of total lesions seen), and 68Ga-DOTATATE demonstrated 332 lesions (96.4 %). The mean SUVmax of all lesions was not significantly different between 68Ga-HA-DOTATATE and 68Ga-DOTATATE (17.8±11.4 vs. 16.7±10.7, n.s.). Conclusion: Our analysis demonstrated very good concordance between 68Ga-HA-DOTATATE and 68Ga-DOTATATE PET data. As the availability and use of 68Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other 68Ga-labelled hsst analogues.