Anna Rizzello

Influence of Trigger PSA and PSA Kinetics on 11C-Choline PET/CT Detection Rate in Patients with Biochemical Relapse After Radical Prostatectomy

The purpose of this study was to investigate the effect of total prostate-specific antigen (PSA) at the time of 11C-choline PET/CT (trigger PSA), PSA velocity (PSAvel), and PSA doubling time (PSAdt) on 11C-choline PET/CT detection rate in patients treated with radical prostatectomy for prostate cancer, who showed biochemical failure during follow-up. Methods: A total of 190 patients treated with radical prostatectomy for prostate cancer who showed an increase in PSA (mean, 4.2; median, 2.1; range, 0.2–25.4 ng/mL) were retrospectively enrolled. All patients were studied with 11C-choline PET/CT. Patients were grouped according to trigger PSA (PSA ≤ 1 ng/mL, 1 < PSA ≤ 2 ng/mL, 2 < PSA ≤ 5 ng/mL, and PSA > 5 ng/mL). In 106 patients, data were available for calculation of PSAvel and PSAdt. Logistic regression analysis was used to determine whether there was a relationship between PSA levels and PSA kinetics and the rate of detection of relapse using PET. Results: 11C-choline PET/CT detected disease relapse in 74 of 190 patients (38.9%). The detection rate of 11C-choline PET/CT was 19%, 25%, 41%, and 67% in the 4 subgroups—PSA ≤ 1 ng/mL (51 patients), 1 < PSA ≤ 2 ng/mL (39 patients), 2 < PSA ≤ 5 ng/mL (51 patients), and PSA > 5 ng/mL (49 patients)—respectively. Trigger PSA values were statistically different between PET-positive patients (median PSA, 4.0 ng/mL) and PET-negative patients (median PSA, 1.4 ng/mL) (P = 0.0001). Receiver-operating-characteristic analysis showed an optimal cutoff point for trigger PSA of 2.43 ng/mL (area under the curve, 0.76). In 106 patients, PSAdt and PSAvel values were statistically different between patients with PET-positive and -negative scan findings (P = 0.04 and P = 0.03). The 11C-choline PET/CT detection rate was 12%, 34%, 42%, and 70%, respectively, in patients with PSAvel < 1 ng/mL/y (33 patients), 1 < PSAvel ≤ 2 ng/mL/y (26 patients), 2 < PSAvel ≤ 5 ng/mL/y (19 patients), and PSAvel > 5 ng/mL/y (28 patients). The 11C-choline PET/CT detection rate was 20%, 40%, 48%, and 60%, respectively, in patients with PSAdt > 6 mo (45 patients), 4 < PSAdt ≤ 6 mo (20 patients), 2 < PSAdt ≤ 4 mo (31 patients), and PSAdt ≤ 2 mo (10 patients). There was no statistical difference between PET-positive and -negative scan detection rates according to the Gleason score, pT and N status, patient age, or duration between surgery and biochemical relapse. Trigger PSA and PSAvel were found to be independent predictive factors for a PET-positive result (P = 0.002; P = 0.04) and PSAdt was found to be an independent factor only in patients with trigger PSA less than 2 ng/mL (P = 0.05) using multivariate analysis. Conclusion: The 11C-choline PET/CT detection rate is influenced by trigger PSA, PSAdt, and PSAvel. This finding could be used to improve the selection of patients for scanning by reducing the number of false-negative scans and increasing the detection rate of disease in patients with early relapse and potentially curative disease.

Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

Purpose18F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18F-DOPA and 68Ga-DOTA-NOC are more accurate for disease assessment and 68Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET.AimThe aim of this study was to compare 68Ga-DOTA-NOC and 18F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours.Materials and methodsThirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18F-DOPA and 68Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging).ResultsThe most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18F-DOPA PET was positive in 9/13. On a lesions basis, 68Ga-DOTA-NOC identified more lesions than 18F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18F-DOPA identified the primary only in two of eight cases.ConclusionsAlthough the patients studied are few and heterogeneous, our data show that 68Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18F-DOPA.

Synthesis and quality control of 68Ga citrate for routine clinical PET.

Introduction and aimScintigraphic imaging of infection and inflammation with 67Ga-citrate is an established and powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. 68Ga is a short-lived positron-emitting radionuclide (half-life 67.6 min, positron energy 2.92 MeV), which allows better imaging qualities than 67Ga using the high spatial resolution and the quantitative features of PET. The aim of this study was to develop a method of synthesis for 68Ga citrate with high and reproducible radiochemical yield using a commercial 68Ga-labelling module. The resultant 68Ga citrate would be suitable for use in the detection of infectious or inflammatory diseases in routine clinical practice. MethodsA simplified method of producing 68Ga citrate is described. Radiochemical purity, pyrogen testing were performed as per the standard protocols. ResultsAfter performing 10 syntheses of 68Ga citrate, the radiochemical yield was 64.1±6.0% (mean±standard deviation) with an average activity of 971.2±103.4 MBq available for labelling. Radiochemical purity determined by instant thin-layer chromatography-silica gel was higher than 98%. All the synthesized products were found to be sterile and pyrogen-free. In this study, the quality control step provided good and reproducible results. This is worth noting, especially in view of the stringent new rules adopted in most European countries for the in-house good manufacturing practice (GMP) synthesis of radiopharmaceuticals. ConclusionThe high radiochemical yield and purity showed that this method is a reliable tool for the production of 68Ga citrate to be used in the detection of inflammatory and infectious diseases using high resolution and qualitative PET.

Radiolabelling, quality control and radiochemical purity assessment of the Octreotide analogue 68Ga DOTA NOC

Somatostatin receptors 1-5 are over expressed in neuroendocrine tumours (NETs). 68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide (DOTA NOC), a recent synthesized somatostatin analogue, shows high affinity for those receptors. Herein, modifications of a commercial module for the labelling of DOTA NOC with 68Ga, as well as the assessment of time course of the radiochemical purity variation are described. The evaluation of radiochemical stability was done by two different chromatographic methods: reversed-phase radio HPLC and fast TLC analysis. Labelled compound has been found radiochemically stable within 3h from the end of labelling (EOL) and radiochemical purity was always higher than 99%. After 73 labelling sessions the system showed great reproducibility and high radiochemical yield.

Small animal PET for the evaluation of an animal model of genital infection

Background:  [18F]‐FDG is a widely used tracer for the non‐invasive evaluation of hypermetabolic processes like cancer and inflammation. However, [18F]‐FDG is considered inaccurate for the diagnosis of urinary tract and genital infections because of its urinary excretion. Since the 1970s, Gallium scintigraphy is a well established test that has been used for the evaluation of inflammation and infection in human patients.

Development of a modular system for the synthesis of PET [11C]labelled radiopharmaceuticals

[((11))C]labelled radiopharmaceuticals as N-[(11)C]methyl-choline ([(11)C]choline), l-(S-methyl-[(11)C])methionine ([(11)C]methionine) and [(11)C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [(11)C]choline, [(11)C]methionine and [(11)C]acetate using components that account for straightforward scaling up and upgrades.

Reliability and reproducibility of N-[11C]methyl-choline and L-(S-methyl-[11C])methionine solid-phase synthesis: a useful and suitable method in clinical practice.

Background and objectiveN-[11C]methyl-choline ([11C]choline) and L-(S-methyl-[11C])methionine ([11C]methionine) are PET radiopharmaceuticals which have gained interest as oncological tracers. The increasing demand of these radiopharmaceuticals needs robust methods of synthesis with high and reproducible yield which provide enough activity for multiple patient administration in a short synthesis time. MethodsDifferent synthetic approaches have been described in the literature but exhaustive reports on performance and reliability of different methods have not been described yet. Results and conclusionIn the present study, we demonstrated the reliability and reproducibility of the solid-phase [11C]methylation method for the synthesis of [11C]choline and [11C]methionine as a suitable tool for the routine clinical use.

Acceptance Tests and Quality Control of Ge/ Ga Generators

In this paper we describe test methods useful to evaluate the performance of Ge/ Ga generators and to assess radionuclidic purity of the eluates. In our tests on the elution profile of the generator, we found that less than 8.0 ml are sufficient to recover > 98 % of the activity. Elution yield was conforming the manufacturer specifications, being initially > 85 % and still > 64 % after 7 months of use. 68Ge breakthrough in the eluates was limited; even if radionuclidic purity was > 99.99 % , further analyses, in addition to physical tests, is recommended in order to assess chemical impurities that could determine interferences in labelling procedures.

Automated synthesis of [11C]meta hydroxyephedrine, a PET radiopharmaceutical for studying sympathetic innervation in the heart

PET imaging of the sympathetic innervation of the heart can involve the labelling of catecholamine analogues as [11C]meta-hydroxyephedrine ([11C]MHED) which allows the study of adrenergic neurons in heart diseases. Aim of this study was the development of an automatic synthesis program for [11C]MHED using a computer-assisted [11C]methylation module which provides the production and the purification of this radiopharmaceutical with reproducible radiochemical yield for cardiological studies in clinical PET. Radiochemical yield of [11C]MHED was 12 plusmn 1% (n=5) (decay corrected referred to the end of bombardment) with an average production of 3.1 GBq for patient administration. Radiochemical purity was always higher than 99%. These preliminary results show that this computer-assisted approach for the synthesis of radiopharmaceuticals represents a reliable tool for [11C]MHED production in clinical PET.