Preliminary Study On Early Accurate Diagnosis Of Neuroendocrine Tumors And Targeted Therapy With Radionuclid

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Dual-tracer 18F-FDG and 68Ga-DOTA-TATE PET/MRI in the Diagnosis of Hormone-Producing Pituitary MicroadenomaObjective:This study was designed to evaluate the ability of positron emission tomography/magnetic resonance imaging(PET/MRI),using 18F-FDG and 68Ga-DOTA-TATE as tracers,to detect hormone-producing pituitary microadenoma when diagnosis is difficult using MRI alone.Methods:We recruited 37 patients with elevated hormone levels,including 19 with undiagnosable primary pituitary adenoma and 18 with suspected recurrent pituitary adenoma.18F-FDG PET/MRI and 68Ga-DOTA-TATE PET/MRI were performed within 1 week of each other in all patients.Within 2 weeks afterward,27 of the 37 patients underwent trans-sphenoidal adenomectomy,3 underwent sella region radiotherapy,1 underwent somatostatin therapy,and 6 had only clinical follow-up.The image characteristics and uptake levels were correlated with the surgical findings and pathologic results.Receiver-operating-characteristic curves were analyzed to determine the optimal cutoff to differentiate adenoma from normal pituitary tissue.The area under the receiver-operating-characteristic curve was calculated to compare diagnostic performance.Results:The PET/MR images were of diagnostic quality and without obvious image artifacts.The high contrast of the PET images provided complementary information to the fine anatomic display of the MR images.Increased 18F-FDG uptake was clearly observed in all patients.MRI enhanced using a 0.05 mmol/kg dose of gadopentetate dimeglumine showed suggestive findings in only 47%of the patients with primary adenoma and 39%of those with recurrent adenoma;when a 0.1 mmol/kg dose was used,the respective percentages were 37%and 50%.The 18F-FDG SUVmax of the 16 primary adenomas that underwent transsphenoidal adenomectomy(6.8 ±3.7)was significantly higher than that of normal pituitary tissue(3.2±1.1,P<0.01).The adenomas showed moderate 68Ga-DOTA-TATE uptake(SUVmax,3.8±2.6),but the 68Ga-DOTA-TATE uptake was generally lower than that of normal pituitary tissue(SUVmax,6.2±3.2,P<0.05).In the 11 suspected recurrent pituitary adenomas that underwent transsphenoidal adenomectomy,the 18F-FDG SUVmax was 6.1 ±3.5,significantly higher than that of normal pituitary tissue(2.5±1.1,P<0.01),and the 68Ga-DOTA-TATE SUVmax was 3.0± 1.1,significantly lower than that of normal pituitary tissue(5.5± 1.7,P<0.01).The 18F-FDG/8Ga-DOTA-TATE SUVmax ratio of the adenomas(2.3 ± 1.5)was significantly higher than that of normal pituitary tissue(0.6 ±0.3,P<0.05).When the 18F-FDG SUVmax alone and the18F-FDG/68Ga-DOTA-TATE SUVma,ratio were used as criteria to discriminate between adenoma and pituitary tissue,the best analysis came from the ratio,and that from 18F-FDG SUVmax alone was only slightly less,with optimal diagnostic cutoffs of 1.04 and 3.88,respectively.Conclusions:PET/MRI provides an ideal tool for the detection of hormone-producing pituitary microadenoma.Dual-tracer 18F-FDG and 68Ga-DOTA-TATE PET/MRI seems better than 18F-FDG PET/MRI alone for distinguishing pituitary microadenoma from normal pituitary tissue.Project ? 18F-FDG PET/MRI versus 18F-FDG PET/CT in Detection of Functioning Pituitary Microadenoma with Inconclusive MRI FindingsObjetive:MRI may be insufficient to locate functioning pituitary microadenoma.This study aims to compare the usefulness of 18F-FDG PET/MRI with that of 18F-FDG PET/CT for detection of functioning pituitary microadenoma in patients with inconclusive conventional MRI findings using contrast-enhanced MRI.Methods:With IRB approval and informed consent,59/97 and 57/97 patients with elevated pituitary hormone levels but inconclusive MRI findings were recruited to undergo 18F-FDG PET/CT and 18F-FDG PET/MRI,respectively.Among them,19 patients underwent both scans.Then,77 patients accepted transsphenoidal adenomectomy within 2 weeks and pituitary microadenomas were confirmed by surgical and pathologic findings in 69 patients.The contrast-enhanced MRI,18F-FDG PET/CT,18F-FDG PET/MRI of these 69 patients were compared and correlated with the surgical and pathological findings.Results:Out of these 69 patients,contrast-enhanced MRI revealed inconclusive findings in 30(66%)of the 45 patients who underwent 18F-FDG PET/CT,which alone provided a definitive diagnosis for 23(51%)patients.By combining contrast-enhanced MRI and 18F-FDG PET/CT,the confidential diagnostic sensitivity achieved 31/45(68%)patients.Among the 40/69 patients who underwent 18F-FDG PET/MRI,15(37%)had suspicious lesions on contrast-enhanced MRI,whereas 35(87%)were definitively diagnosed by PET/MRI.Comparing the two groups of patients,the detection rate for pituitary microadenoma was significantly higher with PET/MRI than with PET/CT(P<0.01).For those who underwent both imaging procedures,PET/MRI provided a definitive diagnosis in 14/16(87%)patients,while PET/CT showed obvious lesions in only 7/16(43%)patients.Conclusions:This study provides direct evidence about the effectiveness of 18F-FDG PET/MRI over 18F-FDG PET/CT for the detection of functioning pituitary microadenoma.Project ? Preliminary Study of 177Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine NeoplasmObjective:A novel radiolabeled somatostatin analogue,177Lu-1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid-Evans blue-Tyr3-octreotate(177Lu-DOTA-EB-TATE),is designed as a theranostic agent based on octreotate but used an Evans blue structure to bind albumin to improve the pharmacokinetics and pharmacodynamics.The aim of this study was to evaluate the dosimetry,safety,and efficacy of 177Lu-DOTA-EB-TATE in treatment of patients with advanced metastatic neuroendocrine neoplasms(NEN).Methods:Eight patients(6 males and 2 females;age range,28?62 y)with advanced metastatic NEN were recruited.Within one week after whole-body 68Ga-DOTA-TATE PET/CT,5 patients accepted a single dose 0.35?0.70 GBq(9.5?18.9 mCi)of 177Lu-DOTA-EB-TATE,and then they underwent serial whole body planar and single-photon emission computed tomography/computed tomography(SPECT/CT)scans at 2,24,72,120 and 168h after injection.The other 3 patients accepted intravenous injection of 0.28?0.41 GBq(7.5?11.1 mCi)of 177Lu-DOTA-TATE for the same imaging acquisition procedures at 1,3,4,24 and 72 h after injection.The dosimetry was calculated using the OLINDA/EXM 1.1 software.After the dosimetry study,4 NEN patients underwent 177Lu-DOTA-EB-TATE treatment with a dose of 1.78 ± 0.21 GBq(48.3 ± 5.7 mCi);3 other NEN patients enrolled as controls underwent 177Lu-DOTA-TATE treatment with administered activity of 3.98±0.17 GBq(107.6±4.6 mCi).The 7 patients were reevaluated with 68Ga-DOTA-TATE PET/CT after the treatment.Maximum SUV(SUVmax)of the tumours ?2.0 cm in diameter were measured and percentage of change(?SUV)after treatment were calculated.Results:The administered dose of 177Lu-DOTA-EB-TATE was well tolerated,with no adverse symptoms reported during the 5-month follow-up in any of the patients.Compared with 177Lu-DOTA-TATE,177Lu-DOTA-EB-TATE showed much higher radioactivity accumulation in NEN tumors,as well as prolonged circulation in the blood.The total body effective doses were 0.2048 ± 0.1605 mSv/MBq for 117Lu-DOTA-EB-TATE and 0.1735 ±0.0722 mSv/MBq for 177Lu-DOTA-TATE.Dose delivery of 177Lu-DOTA-EB-TATE to the kidneys and bone marrow were 3.2-fold and 18.2-fold of that of 177Lu-DOTA-TATE,respectively.Whereas 177Lu-DOTA-EB-TATE achieved 7.9-fold tumor dose delivery than that of 177Lu-DOTA-TATE.All 4 patients showed symptomatic remission to a single low dose 177Lu-DOTA-EB-TATE treatment.Among the patients,40 tumours were found with diameter ?2.0 cm,with the baseline SUVmax varied from 1.5?82.9(35.9±21.0)and the ? SUVs 3 months later were from-75.1%?26.3%(-38.9%±25.5%).Twenty-nine(72.5%)of the tumours showed>15%decrease of SUVmax(? SUV=-75.1%?17.1%).There was a significant negative correlation between the baseline SUVmax and the ? SUV after treatment(r=-0.852,P<0.001).Compared with the control 177Lu-DOTA-TATE therapy,the 177Lu-DOTA-EB-TATE treatment using approximately 1/6 of the doses showed similar response in ASUV(-7.9%±5.4%vs.-5.8%±33.9%,P=0.189)as demonstrated by the tumours with comparable baseline SUVmax from 10.0?35.0.Two months after thetherapy dose of 177Lu-DOTA-EB-TATE treatment,2 patients showed further decrease of summed target lesions.Conclusion:This first-in-human study demonstrates that 177Lu-DOTA-EB-TATE is safe and well tolerated in NEN patients.Remarkably higher 177Lu-DOTA-EB-TATE uptake and longer retention was found in NEN tumors,with the increase of delivery dose much higher than that of the kidneys,which merit similar therapeutic effects with lower doses.