Diana Salvo

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

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.

Clinical Applications of Positron Emission Tomography (PET) Imaging in Medicine: Oncology, Brain Diseases and Cardiology

Positron Emission Tomography (PET) is a diagnostic imaging procedure used regularly to acquire essential clinical information. The PET – CT hybrid, which consists of two scanning machines: PET scanner and an x-ray Computed Tomography (CT). At present these represent the technological hierarchy of Nuclear Medicine, occupying an important position in diagnostics. In fact, PET – CT has the capability to evaluate diseases through a simultaneous functional and morphostructural analysis. This allows for an earlier diagnosis of the disease state which is crucial for obtaining the required information to provide a more reliable prognosis and therapy. Presently, the most frequently used PET radiotracer [18F]fluorodeoxyglucose (FDG) has a major role in oncology. Useful information is being regularly obtained by using both FDG and a selection of radiotracer compounds to evaluate some of the most important biological processes. Thus, creating an opening for ‘Molecular Imaging’ and providing a platform for a potential revolution in the clinical diagnostic field. In this review, we hope to present the most interesting technicalogical and methodological advances in clinical diagnostics for oncology, neurology, and cardiology. A particular attention is dedicated to the applications of PET in neuropsychiatric diseases and its connections with receptor imaging.

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

ObjectiveBeta-emitting radionuclides are being increasingly used in targeted radionuclide therapy in nuclear medicine. In particular, the pure high-energy &bgr;-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 &bgr;-dosimetry data related to therapeutic 90Y-labelled DOTA-D-Phe1-Tyr3-octreotide preparation and administration in a nuclear medicine department. MethodsPersonal dose measurements were carried out with a series of thin active layer ultrasensitive MCP-Ns (LiF: Mg, Cu, P) dosimeters fixed at the operators fingertips and by means of some direct reading dosimeters; other individual protection devices, such as shielded aprons and anti-X gloves, were also used. ResultsThe 95th percentile of the chemists 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 physicians 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). ConclusionBecause of the physical properties of &bgr;-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.

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.

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.

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.

Three-dimensional display of myocardial perfusion detection of ischemic lesions using a new image subtraction method

A recent, commercially available computer program for the three-dimensional (3D) display of single-photon emission tomography (SPET) data was used to study myocardial perfusion in patients with coronary artery disease (CAD). To enable the detection of small ischemic lesions, the authors proposed a new “distance-subtraction” method: after suitable centering of the axial slices, 3D “distance-shaded” images of the stress study were subtracted from the corresponding views of the rest study. With this technique, small changes in surface-to-observer distance were highlighted, thus enabling us to detect nontransmural ischemic areas of the myocardium. General characteristics and possibilities of the subtraction technique were tested on a simple myocardial phantom. Some clinical results of the application of this method on CAD patients are presented and discussed. In CAD patients in whom only nontransmural ischemic lesions are present, the subtraction of “distance-shaded” images is decisive for a correct diagnosis.

Pulmonary deposition of aerosolised pentamidine using a new nebuliser: efficiency measurements in vitro and in vivo

The therapeutic efficacy of nebulised pentamidine in the prophylaxis of Pneumocystis carinii pneumonia (PCP) depends on the absolute pulmonary deposition of the drug. We studied the performance of a new nebuliser (Pentasave) by comparison both in vitro and in vivo with a standard nebuliser (Respirgard 11). In vitro, deposition of pentamidine labelled with technetium-99m human serum albumin was measured indirectly by capturing inhaled particles on an absolute filter and measuring radioactivity with a gamma camera. The nebulisers were initially assessed with a pentamidine dose of 100 mg in 5 ml at 44 psi and an air flow of 101/min for Respirgard II and 16 1/min for Pentasave. Nebuliser output, expressed as the percentage of the initial nebuliser radioactivity captured by the inhalation filter, was 15%±2% (mean±SD) for Respirgard 11, and significantly increased to 23%±3% for an initial version and to 33%±2% for the final version of Pentasave. Measurements with a gamma camera in a group of ten patients with human immunodeficiency virus infection were made in vivo. The results revealed that pulmonary drug distributions are good using both Respirgard II and Pentasave. The literature reports that once-monthly pulmonary deposition of 9 mg pentamidine seems enough to produce prophylactic effects against Pneumocystis carinii. We measured pulmonary pentamidine deposition of 20.22±4.31 mg (mean ±SD) using Respirgard 11 (with 300 mg in 5 m1) and of 16.00±7.18 mg using Pentasave (with 150 mg in 6 ml). These findings show that the therapeutic dose of pentamidine (9 mg) was widely exceeded with both nebulisers. Further investigations might demonstrate that about 200 mg and 125 mg pentamidine for Respirgard II and Pentasave, respectively, will achieve a pulmonary deposition of therapeutic dose, allowing significant savings in terms of drug and expense.

Dynamic lymphadenoscintigraphy of the lower limbs

SummaryThe use of dynamic lymphadenoscintigraphy is proposed for the study of the lymphatic flow in the lower limbs. The method is based on the determination of the flow curves of radiocolloid (antimony-sulphide labelled with99mTc) in the lower limbs, on the time of its appearance in the inguinal lymphatic vessels and in the liver, and also on the recording by periodically repeated photoscans of the progress of the radiocolloid in the pre-lymph node ducts. Thus, the method is suggested for use in the observation of flow variations as an expression of metastatic or systemic lymph node diseases and in the differential diagnosis of lymphatic and venous oedema.