Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions.

The DOTA macrocyclic ligand can form stable complexes with many cations besides yttrium and lutetium. For this reason, the presence of competing cationic metals in yttrium-90 and lutetium-177 chloride solutions can dramatically influence the radiolabeling yield. The aim of this study was to evaluate the coordination yield of yttrium- and lutetium-DOTATATE complexes when the reaction is performed in the presence of varying amounts of competing cationic impurities. In the first set of experiments, the preparation of the samples was performed by using natural yttrium and lutetium (20.4 nmol). The molar ratio between DOTATATE and these metals was 1 to 1. Metal competitors (Pb(2+), Zn(2+), Cu(2+), Fe(3+), Al(3+), Ni(2+), Co(2+), Cr(3+)) were added separately to obtain samples with varying molar ratio with respect to yttrium or lutetium (0.1, 0.5, 1, 2 and 10). The final solutions were analyzed through ultra high-performance liquid chromatography with an UV detector. In the second set of experiments, an amount of (90)Y or (177)Lu chloride (6 MBq corresponding to 3.3 and 45 pmol, respectively) was added to the samples, and a radio-thin layer chromatography analysis was carried out. The coordination of Y(3+) and Lu(3+) was dramatically influenced by low levels of Zn(2+), Cu(2+) and Co(2+). Pb(2+) and Ni(2+) were also shown to be strong competitors at higher concentrations. Fe(3+) was expected to be a strong competitor, but the effect on the incorporation was only partly dependent on its concentration. Al(3+) and Cr(3+) did not compete with Y(3+) and Lu(3+) in the formation of DOTATATE complexes.

Ga-68 DOTATOC PET, endoscopic ultrasonography, and multidetector CT in the diagnosis of duodenopancreatic neuroendocrine tumors: a single-centre retrospective study.

PURPOSE: In this report, we compared endoscopic ultrasonography (EUS), multidetector CT (MDCT), and Ga-68 DOTATOC PET/CT in patients with neuroendocrine tumors (NETs). We report our experience with use of these methods in patients suspected to have duodenopancreatic primitive NET. METHODS: Nineteen consecutive patients (mean age, 56; 21-80), who underwent both Ga-68 DOTATOC PET/CT and EUS between March 2007 and November 2008 were retrospectively included in the study (16 underwent MDCT). Suspicion of NET was confirmed by EUS-FNA and/or surgery. Operative characteristics of PET, EUS, and MDCT were compared. RESULTS: Twenty-three neuroendocrine lesions were diagnosed in 13/19 patients. EUS, PET, and MDCT correctly identified as affected 13/13 (100%), 12/13 (92%), and 10/11 (91%) patients, respectively. On a lesion basis, EUS, PET, and MDCT identified correctly as NETs 22/23 (96%), 20/23 (87%), and 13/18 (72%) lesions (P = 0.08 EUS vs. CT). Both on a patient and on a lesion basis, specificity was 67%, 83%, and 80% for EUS, PET, and MDCT, respectively. CONCLUSIONS: EUS, Ga-68 DOTATOC PET, and MDCT seem to have comparable accuracy in diagnosis of duodenopancreatic NET and their combination may allow an optimal preoperative diagnosis.

Efficient automated one-step synthesis of 2-[18F]fluoroethylcholine for clinical imaging: optimized reaction conditions and improved quality controls of different synthetic approaches.

UNLABELLED: [(18)F]-labelled choline analogues, such as 2-[(18)F]fluoroethylcholine ((18)FECH), have suggested to be a new class of choline derivatives highly useful for the imaging of prostate and brain tumours. In fact, tumour cells with enhanced proliferation rate usually exhibit an improved choline uptake due to the increased membrane phospholipids biosynthesis. The aim of this study was the development of a high yielding synthesis of (18)FECH. The possibility of shortening the synthesis time by reacting all the reagents in a convenient and rapid one-step reaction was specially considered. METHODS: (18)FECH was synthesized by reacting [(18)F]fluoride with 1,2-bis(tosyloxy)ethane and N,N-dimethylaminoethanol. The synthesis was carried out using both a one- and a two-step reaction in order to compare the two procedures. The effects on the radiochemical yield and purity by using different [(18)F]fluoride phase transfer catalysts, reagents amounts and purification methods were assessed. Quality controls on the final products were performed by means of radio-thin-layer chromatography, gas chromatography and high-performance liquid chromatography equipped with conductimetric, ultraviolet and radiometric detectors. RESULTS: In the optimized experimental conditions, (18)FECH was synthesized with a radiochemical yield of 43+/-3% and 48+/-1% (not corrected for decay) when the two-step or the one-step approach were used, respectively. The radiochemical purity was higher than 99% regardless of the different synthetic pathways or purification methods adopted. The main chemical impurity was due to N,N-dimethylmorpholinium. The identity of this impurity in (18)FECH preparations was not previously reported. CONCLUSION: An improved two-step and an innovative one-step reaction for synthesizing (18)FECH in a high yield were reported. The adaptation of a multistep synthesis to a single step process, opens further possibilities for simpler and more reliable automations.

Radiation protection in 90Y-labelled DOTA-D-Phe1-Tyr3-octreotide preparations.

OBJECTIVE: Beta-emitting radionuclides are being increasingly used in targeted radionuclide therapy in nuclear medicine. In particular, the pure high-energy beta-emitter 90Y (Emax=2.27 MeV) has a physical half-life compatible with the pharmacokinetics of peptides. The use of this isotope implies an increase in the radiation dose received by the nuclear medicine staff. The aim of this study is thus the evaluation of the personal beta-dosimetry data related to therapeutic 90Y-labelled DOTA-D-Phe1-Tyr3-octreotide preparation and administration in a nuclear medicine department. METHODS: Personal dose measurements were carried out with a series of thin active layer ultrasensitive MCP-Ns (LiF: Mg, Cu, P) dosimeters fixed at the operator's fingertips and by means of some direct reading dosimeters; other individual protection devices, such as shielded aprons and anti-X gloves, were also used. RESULTS: The 95th percentile of the chemist's skin equivalent dose distribution was 1.759 mSv/GBq by using 0.10-mm anti-X gloves and 0.265 mSv/GBq by using 0.20-mm anti-X gloves. The 95th percentile of the physician's skin equivalent dose distribution was 1.198 mSv/GBq by using 0.10-mm anti-X gloves. The use of an anti-X apron during administration permits saving absorbed doses by a factor over 97% for both Hp(10) and Hp(0.07). CONCLUSION: Because of the physical properties of beta-emitters, an increased number of therapeutic sessions is to be expected. The dose values measured till now, resulting from a high radioprotection level modus operandi, have always respected the threshold limits reported by the European Directive EURATOM 96/29 05/13/1996 for exposed workers, even in addition to other clinical practices in the department.

Validation of (68)Ge/(68)Ga generator processing by chemical purification for routine clinical application of (68)Ga-DOTATOC.

INTRODUCTION: Imaging of somatostatin receptor expressing tumours has been greatly enhanced by the use of (68)Ga-DOTATOC and PET/CT. METHODS: In this work, a purification method for the (68)Ge/(68)Ga generator eluate and a method to produce (68)Ga-DOTATOC suitable for clinical use were evaluated. The generator eluate was purified and concentrated on a cation-exchange cartridge in HCl/acetone media. The efficacy of this procedure in eliminating metal impurities from the (68)Ga solution was investigated by ICP-MS. The radiotracer quality was evaluated by radio-TLC, GC and gamma-ray spectrometry. RESULTS: (68)Ga-DOTATOC preparations (n=33) were carried out with a mean synthesis yield of 59.3+/-2.8% (not corrected for decay) and a batch activity ranging from 555 to 296 MBq. The radiochemical and radionuclidic purity were >98% and 99.9999%, respectively. With this purification process, >95% of the Fe(III), Zn(II) and Mn(II) were eliminated from the solution. CONCLUSIONS: (68)Ga-DOTATOC produced with this method can be efficiently used in nuclear medicine departments for PET evaluations.

Positron emission tomography (PET): evaluation of chronic periaortitis.

OBJECTIVE: To evaluate the presence and extent of large-vessel inflammation in patients with chronic periaortitis (CP) using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: A consecutive case series consisting of 7 patients with CP seen over a 3-year period and a control group of 14 patients with malignancy were evaluated with FDG-PET. For every case we selected 2 age- and sex-matched controls who underwent PET imaging for malignancy. The diagnosis of CP was made by means of computed tomography. PET imaging was performed at diagnosis before therapy was started. Measurement of vascular uptake was graded using a 4-point semiquantitative scale. RESULTS: All patients had evidence of grade 2+ or 3+ vascular uptake in the abdominal aorta and/or iliac artery. No controls showed vascular uptake greater than 1+. Vascular uptake in the thoracic aorta and/or in its branches was seen in 3 (43%) of 7 patients. Vascular uptake in abdominal aorta and/or iliac artery was observed in patients with CP but not in controls (100% versus 0%). There was also a significantly more frequent FDG uptake in the large thoracic arteries in case-patients compared with controls (43% versus 0%; P = 0.03). CONCLUSION: FDG-PET scan shows in patients with CP the presence of a large-vessel vasculitis involving abdominal aorta and common iliac arteries, which in some patients is also extended to thoracic aorta and/or its branches.

The impact of 18F-deoxyglucose positron emission tomography on tumor staging, treatment strategy and treatment planning for radiotherapy in a department of radiation oncology.

AIMS AND BACKGROUND: The study analyzed the potential contribution of positron emission tomography (PET) in patient selection for radiotherapy and in radiation therapy planning. METHODS: Eighty-seven patients with a histological cancer diagnosis were accrued for the study from December 2000 to December 2001. Demographic characteristics included a median age of 54 years and male/female ratio of 51/36. All patients staged by conventional workup who were candidates for radiotherapy had PET imaging and were allocated to a conventional "pre/post-PET stage". The treatment protocol and the shape and/or size of the portals was directly related to PET results. We examined 26 lung cancers, 15 gastrointestinal tumors, 22 genitourinary cancers and 24 hematologic malignancies. RESULTS: In the lung cancer group, the stage was modified in 10/26 patients (38.5%) by PET, with a change in management in 13 (50%) and a change in radiotherapy planning in 6 (23.1%). In the hematological group, stage was modified by PET in 8/24 cases (33.3%), with a change in treatment strategy in 9 (37.5%) and a change in radiotherapy planning in 3 (12.5%). In the gastrointestinal group, the stage was modified by PET in 2/15 cases (13.4%), with a change inn treatment strategy in 4 (26.7%) and a change in the decision for radiotherapy in 8 (no radiotherapy in 53.3%). In the mixed group (genitourinary, breast and other), the stage was modified by PET in 6/22 cases (27.3%), with a change in treatment strategy in 11 (50%) and a very low rate of change in radiotherapy planning. CONCLUSIONS: PET contributed to a modification of stage in 26/87 patients (30%), to a changing in treatment strategy in 37/87 (42.5%), and to a substantial change of the shape and/or size of radiotherapy portals in 13/43 (30%) who underwent radiotherapy.

Diagnosis of neck recurrences in patients with differentiated thyroid carcinoma.

BACKGROUND: The follow-up of patients with differentiated thyroid carcinoma (DTC) is traditionally carried out with (131)I whole body scan ((131)I WBS) and serum thyroglobulin (Tg) measurement. Neck ultrasonography (US) is also used. METHODS: We compared the roles of Tg measurement (IRMA assay) after l-thyroxine (T4) withdrawal, (131)I WBS, and US in the diagnosis of DTC neck recurrences. Diagnosis of DTC neck recurrences was based on fine-needle aspiration biopsy (FNAB) or on histologic results. Four hundred ninety-four DTC patients (120 males, 374 females; mean age, 49.3 years), submitted to total thyroidectomy and subsequent radioablative (131)I treatment, underwent serum Tg measurement off T4 therapy, (131)I WBS, and neck US at our institution. Mean (+/- SD) follow-up time was 55.1 +/- 37.7 months. Neck DTC recurrences were detected in 51 (10.3%) patients (34 females, 17 males; mean age, 49.5 years). RESULTS: Neck recurrences occurred after 44.6 +/- 21.4 months from initial treatment. Serum Tg levels increased (> or = 2 ng/mL) off T4 therapy in 29 patients (sensitivity 56.8%), (131)I WBS showed neck uptake in 23 patients (sensitivity 45.1%) and coexisting distant metastases were detected in 9 of 23 patients, and US identified neck recurrence in 48 patients (sensitivity 94.1%). Of these 48 neck recurrences, 19 were found in the laterocervical compartment and 29 in the central neck compartment. CONCLUSIONS: Traditional techniques for the surveillance of DTC patients are not as sensitive as US in the detection of neck recurrences. Neck US detects recurrences in patients with undetectable serum Tg levels and negative IWBS and should be performed as the first-line test in the follow-up of all DTC patients.