Evaluation of novel 111In-labeled gonadotropin-releasing hormone peptides for human prostate cancer imaging.

The purpose of this study was to evaluate the tumor targeting and imaging properties of novel 111In-labeled gonadotropin-releasing hormone (GnRH) peptides for human prostate cancer. Three new 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linker-d-Phe-(d-Lys6-GnRH) peptides with different hydrocarbon linkers were designed to evaluate their effects on GnRH receptor binding affinities. The Aoc (aminooctanoic acid) linker was better than ßAla (3-aminopropanoic acid) and Aun (aminoundecanoic acid) linkers in retaining strong receptor binding affinity. DOTA-Aoc-d-Phe-(d-Lys6-GnRH) exhibited 6.6±0.1nM GnRH receptor binding affinity. 111In-DOTA-Aoc-d-Phe-(d-Lys6-GnRH) exhibited fast tumor uptake and urinary clearance in DU145 human prostate cancer-xenografted nude mice. The DU145 tumor lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using 111In-DOTA-Aoc-d-Phe-(d-Lys6-GnRH) as an imaging probe, providing an insight into the design of new GnRH peptides for prostate cancer in the future.

Ethnic comparison of pharmacokinetics of (18)F-florbetaben, a PET tracer for beta-amyloid imaging, in healthy Caucasian and Japanese subjects.

PURPOSE: (18)F-Florbetaben is a positron emission tomography (PET) tracer indicated for imaging cerebral beta-amyloid deposition in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive decline. The present study examined ethnic comparability of the plasma pharmacokinetics, which is the input to the brain, between Caucasian and Japanese subjects. METHODS: Two identical phase I trials were performed in 18 German and 18 Japanese healthy volunteers to evaluate the plasma pharmacokinetics of a single dose of 300 MBq (18)F-florbetaben, either of low (≤5 µg, LD) or high (50-55 µg, HD) mass dose. Pharmacokinetic parameters were evaluated based on the total (18)F radioactivity measurements in plasma followed by metabolite analysis using radio-HPLC. RESULTS: The pharmacokinetics of (18)F-florbetaben was characterized by a rapid elimination from plasma. The dose-normalized areas under the curve of (18)F-florbetaben in plasma as an indicator of the input to the brain were comparable between Germans (LD: 0.38 min/l, HD: 0.55 min/l) and Japanese (LD: 0.35 min/l, HD: 0.45 min/l) suggesting ethnic similarity, and the mass dose effect was minimal. A polar metabolite fraction was the main radiolabelled degradation product in plasma and was also similar between the doses and the ethnic groups. CONCLUSION: Absence of a difference in the pharmacokinetics of (18)F-florbetaben in Germans and Japanese has warranted further global development of the PET imaging agent.

Quantitative Evaluation of mMate1 Function Based on Minimally Invasive Measurement of Tissue Concentration Using PET with [(11)C]Metformin in Mouse.

PURPOSE: To evaluate the function of multidrug and toxin extrusion proteins (MATEs) using (11)C-labeled metformin ([(11)C]metformin) by positron emission tomography (PET). METHODS: PET was performed by intravenous bolus injection of [(11)C]metformin. Pyrimethamine at 0.5 and 5 mg/kg was intravenously administered to mice 30 min prior to the scan. Integration plot analysis was conducted for calculating liver (CLuptake,liver), kidney (CLuptake,kidney) tissue uptake, intrinsic biliary (CLint,bile) and urinary (CLint,urine) excretion clearances of [(11)C]metformin. RESULTS: Visualization by PET showed that pyrimethamine increased concentrations of [(11)C]metformin in the liver and kidneys, and decreased the concentrations in the urinary bladder without changing the blood profiles. Pyrimethamine had no effect on the CLuptake,liver and CLuptake,kidney, which were similar to the blood-flow rate. CLint,bile with regard to the liver concentration was unable to be determined, but administration of 0.5 and 5 mg/kg of pyrimethamine increased the liver-to-blood ratio to 1.6 and 2.3-fold, respectively, indicating that pyrimethamine inhibited the efflux of [(11)C]metformin from the liver. CLint,urine with regard to the corticomedullary region concentrations was decreased 37 and 68% of the control by administration of 0.5 and 5 mg/kg of pyrimethamine, respectively (P < 0.05). CONCLUSIONS: Tissue concentration based investigations using [(11)C]metformin by PET enables the functional analysis of MATEs in the liver and kidneys.

Validation of urinary calcium isotope excretion from bone for screening anabolic therapies for osteoporosis.

SUMMARY: Urinary excretion of calcium tracers in labeled individuals decreases in response to antiresorptive therapy, providing a tool to rapidly screen potential therapies. Using teriparatide, we demonstrate in this study that anabolic therapy also decreases tracer excretion, confirming that this method can also be used to screen potential anabolic therapies. INTRODUCTION: Changes in urinary excretion of calcium tracers from a labeled skeleton may be a rapid and sensitive method to screen potential therapies for osteoporosis. This method has been used to screen antiresorptive therapies, but the effect of anabolic therapies on tracer excretion is unknown. METHODS: Eight-month-old female Sprague Dawley rats (n = 11) were given 50 µCi (45)Ca iv. After a 1-month equilibration period, baseline urinary (45)Ca excretion and total bone mineral content (BMC) were measured. Rats were then treated with 30 µg/kg teriparatide sc per day, a bone anabolic agent, for 80 days. Urine was collected throughout the study and analyzed for (45)Ca and total Ca, and BMC was measured at the beginning and end of the study. RESULTS: Teriparatide decreased urinary (45)Ca excretion by 52.1 % and increased BMC by 21.7 %. The change in bone calcium retention as determined by the ratio of (45)Ca to total Ca excretion in urine from day 6 through 15 of teriparatide treatment was significantly correlated (p = 0.036) with the change in BMC after 80 days of teriparatide treatment. CONCLUSION: Urinary excretion of calcium tracers from labeled bone is an effective method to rapidly screen potential anabolic therapies for osteoporosis.

Gamma camera imaging for studying intestinal absorption and whole-body distribution of selenomethionine.

Se metabolism in humans is not well characterised. Currently, the estimates of Se absorption, whole-body retention and excretion are being obtained from balance and tracer studies. In the present study, we used gamma camera imaging to evaluate the whole-body retention and distribution of radiolabelled selenomethionine (SeMet), the predominant form of Se present in foods. A total of eight healthy young men participated in the study. After consumption of a meal containing 4 MBq [75Se]L-SeMet ([75Se]SeMet), whole-body gamma camera scanning was performed for 45 min every hour over a 6 h period, every second hour for the next 18 h and once on each of the subsequent 6 d. Blood, urine and faecal samples were collected to determine the plasma content of [75Se]SeMet as well as its excretion in urine and faeces. Imaging showed that 87·9 (sd 3·3)% of the administered activity of [75Se]SeMet was retained within the body after 7 d. In contrast, the measured excretion in urine and faeces for the 7 d period was 8·2 (sd 1·1)% of the activity. Time-activity curves were generated for the whole body, stomach, liver, abdomen (other than the stomach and the liver), brain and femoral muscles. Gamma camera imaging allows for the assessment of the postprandial absorption of SeMet. This technique may also permit concurrent studies of organ turnover of SeMet.

Synthesis of multi-galactose-conjugated 2'-O-methyl oligoribonucleotides and their in vivo imaging with positron emission tomography.

(68)Ga labelled 2'-O-methyl oligoribonucleotides (anti-miR-15b) bearing one, three or seven d-galactopyranoside residues have been prepared and their distribution in healthy rats has been studied by positron emission tomography (PET). To obtain the heptavalent conjugate, an appropriately protected 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) precursor bearing a 4-[4-(4,4'-dimethoxytrityloxy)butoxy]phenyl side arm was first immobilized via a base labile linker to the support and the oligonucleotide was assembled on the detritylated hydroxyl function of this handle. A phosphoramidite building block bearing two phthaloyl protected aminooxy groups and one protected hydroxyl function was introduced into the 5'-terminus. One acetylated galactopyranoside was coupled as a phosphoramidite to the hydroxyl function, the phthaloyl protections were removed on-support and two trivalent galactopyranoside clusters were attached as aldehydes by on-support oximation. A two-step cleavage with aqueous alkali and ammonia released the conjugate in a fully deprotected form, allowing radiolabelling with (68)Ga in solution. The mono- and tri-galactose conjugates were obtained in a closely related manner. In vivo imaging in rats with PET showed remarkable galactose-dependent liver targeting of the conjugates.

Maximizing the sensitivity of the indirect radionuclide cystogram: a retrospective audit.

BACKGROUND: The indirect radionuclide cystogram (IRC) has generally been reported as being less sensitive for detecting vesico-ureteric reflux (VUR) than the micturating cystourethrogram (MCUG), so we modified it in an attempt to increase its sensitivity. METHODS: We altered our routine IRC protocol by including the data obtained during failed voids, adding extra imaging sequences at intervals during bladder filling, and by using simple mathematical criteria to determine if VUR was present when visual imaging results were equivocal. We then retrospectively compared the VUR detection rates using the standard and modified techniques. RESULTS: We assessed 707 renal units in 356 children over 3 years. We identified 91 cases of VUR using standard methodology, and 134 (47% more) with the modified technique. Of the extra 43 cases detected, 11 were noted during failed voids, ten were seen within a filling sequence, and 22 were inferred because the renal pelvic activity increased during an interval between two imaging sequences, while the bladder was filling. Mathematical evaluation was helpful in the 39 cases where the increase in activity due to VUR was ≤6 standard deviations greater than the level of background variation in activity. CONCLUSIONS: Additional imaging and mathematical assessment can significantly increase the sensitivity of the IRC for detecting VUR, possibly to equal that of the MCUG.

Intra-arterial treatment with 9°Y microspheres for hepatocellular carcinoma: 4 years experience at the Ghent University Hospital.

PURPOSE: We report on our experience in terms of eligibility, safety, response and survival for treatment of hepatocellular carcinoma (HCC) with (90)Y microspheres. Secondly, we investigated the urinary excretion of (90)Y following treatment. METHODS: We retrospectively reviewed all HCC patients referred to our department for (90)Y microsphere treatment. We recorded reasons for not proceeding to actual treatment. In case treatment was performed, we assessed the tolerance (Common Terminology Criteria for Adverse Events v3.0, CTCAE v3.0), the response [modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria] and long-term survival (Kaplan-Meier). The urinary excretion was estimated by 12-h urine collections post-injection for analysis in a gamma counter. RESULTS: Forty-three HCC patients were referred for radioembolization. Fourteen patients were excluded, mainly due to unfavourable (99m)Tc-macroaggregated albumin (MAA) distribution. Twenty-nine patients were treated with (90)Y microspheres (TheraSphere, mean activity 2.17 GBq). In four patients severe clinical adverse events were encountered, however only in one case clearly related to the therapy. Twenty patients were assessable by mRECIST: complete response in 15%, partial response in 35%, stable disease in 30% and progression in 20% were observed. A median survival of 12.3 months (95% confidence interval 9.4-15.2) was estimated. Concerning the substudy on urinary excretion, only 0.0025% of the administered activity was excreted in the urine within the first 12 h following TheraSphere. CONCLUSION: Following a strict workup before admitting patients to radioembolization with TheraSphere, we found good clinical tolerance in the vast majority of patients. Radiological response assessment yielded an overall response rate of 50%, when evaluated early following treatment. Urine analysis showed consistently only low activities of (90)Y excreted in the urine.

Neopentyl Glycol as a Scaffold to Provide Radiohalogenated Theranostic Pairs of High In Vivo Stability.

The high in vivo stability of 2,2-dihydroxymethyl-3-[18F]fluoropropyl-2-nitroimidazole ([18F]DiFA) prompted us to evaluate neopentyl as a scaffold to prepare a radiotheranostic system with radioiodine and astatine. Three DiFA analogues with one, two, or without a hydroxyl group were synthesized. While all 125I-labeled compounds remained stable against nucleophilic substitution, only a 125I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against in vivo deiodination. 211At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism. 211At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the 125I/211At-labeled benzoate pair. The urine analyses confirmed that 211At-labeled neopentyl glycol was excreted in the urine as a glucuronide conjugate with the absence of free [211At]At-. These findings indicate that neopentyl glycol would constitute a promising scaffold to prepare a radiotheranostic system with radioiodine and 211At.

Identification, Characterization, and Suppression of Side Products Formed during the Synthesis of [177Lu]Lu-PSMA-617.

In recent years, radiolabeled tracers targeting prostate-specific membrane antigen (PSMA) have had a tremendous impact on prostate cancer management. Here, we report on the formation of radioactive impurities formed during the clinical production of 177Lu-labeled PSMA-617. We provide compelling evidence that these impurities are the result of a spontaneous, thermally mediated condensation reaction of the Glu-CO-Lys moiety resulting in the formation of three different five-membered ring systems. Density functional theory (DFT) calculations show that the condensation and cyclization of the Glu-CO-Lys moiety is thermodynamically spontaneous. In cell experiments, no affinity of these cyclized compounds toward PSMA was observed. HPLC analyses of urine samples from patient studies showed rapid renal excretion of these radioactive cyclized species. Radiolabeling conditions were identified that significantly reduced the formation of cyclized side products yielding 177Lu-labeled PSMA-617 in high radiochemical yield and purity in concordance with current good manufacturing practice (cGMP) requirements.

Development and characterization of two novel 68 Ga-labelled neuropeptide Y short analogues with potential application in breast cancer imaging.

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.

High-performance renal imaging with a radiolabeled, non-excretable chimeric fusion protein.

Ideal nuclear imaging tracers should exhibit high target uptake and low background signal. Traditional renal scintigraphy and SPECT scans examine kidney function via static or dynamic tracing of radioactive probes in the kidneys. The lack of tracer affinity to specific biological processes and high background uptake from urinary excretion have added many difficulties to precision renal diagnosis. In this issue of Theranostics, Jin and colleagues innovatively devised a recombinant probe for preferential kidney imaging through targeting of tubular neonatal Fc receptor and proximal tubular basement membrane for sustained tubular reabsorption and accumulation. This work has broad implications regarding how an in depth understanding of physiology and pathology may be of service for tracer development, renal diagnosis, and disease theranostics.

Synthesis, Preclinical Evaluation, and First-in-Human PET Study of Quinoline-Containing PSMA Tracers with Decreased Renal Excretion.

The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate cancer (PCa). In this study, three 18F-labeled PSMA tracers with a more lipophilic quinoline functional spacer were designed, synthesized, and evaluated based on the Glu-Ureido-Lys binding motif. The effect of structure-related lipophilic difference on distribution and excretion of these tracers in vitro and in vivo (cells, rodent, primate, and human) was investigated by comparing with [18F]DCFPyL. There is no significant correlation between the renal elimination and the lipophilicity of the tracers in all species. However, the higher the lipophilicity of tracer, the higher the radioactivity accumulation in the liver of primate and human, and the less radioactivity is to excrete to the bladder with urine. The screened tracer [18F]8c, with a Ki value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.

High detection rate in [18F]PSMA-1007 PET: interim results focusing on biochemical recurrence in prostate cancer patients.

OBJECTIVE: 18F-labeled prostate-specific membrane antigen (PSMA) ligand, [18F]PSMA-1007, has the benefit of a higher synthetic yield and minimal excretion in the urine. High detection efficacy was reported in biochemical recurrence (BCR) of prostate cancer after radical prostatectomy. Thus, we evaluated the preliminary diagnostic utility of [18F]PSMA-1007 PET in patients with prostate cancer, focusing on the BCR which is not detected on conventional imaging. METHODS: We enrolled a total of 28 patients (age 51-79 years) with BCR of prostate cancer. BCR was defined as a continuous increase in PSA after radical prostatectomy or radiation therapy without any apparent recurrent lesions on conventional diagnostic imaging (CT and bone scintigraphy). PSMA-PET scanning was performed approximately 60 min after intravenous injection of [18F]PSMA-1007 (259 ± 37 MBq). PSMA-PET images were evaluated for lesion detection as well as its relation to PSA values and location. RESULTS: Abnormal uptake, which was suspected to be recurrence or metastasis, was detected in 92.9% (26/28) of patients with BCR. The SUVmax was 8.4 ± 6.4 in local recurrence, 11.5 ± 11.8 in pelvic lymph nodes (LN), and 4.1 ± 1.6 in bone metastasis. The detection rates were 66.7% in the PSA group-1 (0.1-0.5 ng/mL), 85.7% in the PSA group-2 (0.5-1.0 ng/mL), and 100% in the PSA group-3 (above 1.0 ng/mL). Among the PET-positive BCR patients (n = 26), local recurrence was detected in 57.7% (15/26), pelvic LN in 42.3% (11/26), and bone metastasis in 15.4% (4/26). In 53% (8/15) of BCR patients who were suspected of local recurrence, focal uptake was detected adjacent to the bladder on [18F]PSMA-1007 PET. This suggested the significant advantage of having minimal physiological urine excretion. CONCLUSIONS: [18F]PSMA-1007 PET showed a high detection rate in recurrent and metastatic lesions. In patients with BCR, its high detection led to suitable treatment strategies, such as salvage radiation therapy or surgical removal of recurrent lymph nodes. TRIAL REGISTRATION: (UMIN Clinical Trials Registry) UMIN000037697.

[Comparison of four methods for measuring glomerular filtration rate by inulin clearance in healthy individuals and patients with renal failure]. / Comparación de cuatro métodos de medición de la tasa de filtración glomerular con depuración de inulina en individuos sanos y en pacientes con insuficiencia renal.

BACKGROUND: A proper measurement of renal function is important for diagnosis and stratification of kidney disease. Several methods have been used to predict glomerular filtration rate, however the results have been variable depending on the population studied. We aimed to compare the performances of 4 glomerular filtration rate tests with inulin clearance in patients with chronic renal insufficiency and in healthy subjects. METHODS: Inulin clearances performed in 51 individuals with stable renal function were selected. For each of them, we computed 4 estimates: the 24-hour creatinine clearance, technetium (99mTc-DTPA) clearance, Cockcroft-Gault and Levey formulas. Their respective performance was assessed by correlation (Pearson's correlation coefficient) and agreement (Bland and Altman method). RESULTS: Each glomerular filtration rate test closely correlated with inulin clearance. Nevertheless, all GFR tests displayed considerable lack of agreement with lower limits ranging from 15 to 42 ml / min, for comparison with inulin-technetium and inulin with Levey formula, respectively and upper limits of agreement that could range from 20 to 56 ml / min, for comparison with inulin-technetium and Inulin with Levey formula,respectively. CONCLUSION: The measurement of glomerular filtration rate determined via different methods shows a wide range of variation when compared with inulin clearance, which should be considered in daily clinical practice during the evaluation of renal function.

[Treatment with (131)I of thyroid remnants in a patient with papillary thyroid carcinoma and end-stage chronic renal failure]. / Tratamiento con (131)I de restos tiroideos en paciente con carcinoma papilar de tiroides e insuficiencia renal crónica terminal.

The follow-up and treatment of thyroid cancer presents several aspects subject to discussion, such as its management in patients with End-Stage Renal Failure (ESRF). We present a patient with ESRF and papillary thyroid carcinoma, which had to be coordinated among different departments (Endocrinology, Nuclear Medicine, Nephrology and Physics and Radiation Protection). Both the diagnostic scintigraphy with (123)I and the ablative treatment with (131)I performed later were performed with the administration of rh TSH. The room in which the metabolic therapy was to be performed was prepared for the patient's periodic hemodialysis. The (131)I dose used was 80% of the usual dose. This made it possible to assure the therapeutic effect and that the patient's stay in hospital would only be for 5 days. Throughout the whole diagnostic and therapeutic process, no adverse effects attributable to rh TSH or radioiodine were observed. The coordination among the departments involved enabled an effective and safe process for the patient.

Does Delayed Excretion of Therapeutic 131I-MIBG Interfere with a 123I-MIBG Diagnostic Scan 6 Weeks After the Therapy?

131I-metaiodobenzylguanidine (131I-MIBG) is a theranostic agent useful for treatment of neuroendocrine malignancies. In this case, a child with a Curie score of 21 was administered 17.871 GBq (483 mCi) of 131I-MIBG. The elimination half-life progressively increased from 23 h to 77 h during the 11 d that the patient was hospitalized for radiation isolation. Six weeks after the posttherapy scan, a survey with an ion-chamber device yielded readings of 0.3 µSv/h (0.03 mR/h) on contact with spinal regions that had shown increased uptake on the scan. A planar image obtained using the 131I setting and a high-energy collimator did not demonstrate any focal uptake. 123I-MIBG was administered, and the 24-h scan was of diagnostic quality, without degradation from the remaining 131I-MIBG. Additional study is needed on whether the Curie score affects elimination of 131I-MIBG and on whether the period of hospitalized radiation isolation needs to be extended.

Phase I clinical study with different doses of 99mTc-TRODAT-1 in healthy adults.

OBJECTIVES: To study the pharmacokinetics, biodistribution, and injection doses of 99mTc-TRODAT-1 in healthy adults. METHODS: Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of 99mTc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively. RESULTS: No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that 99mTc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10-3 mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10-3 mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088). CONCLUSIONS: 99mTc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.

Standardization of acquisition protocols using PET/CT with 18F-Choline in prostate cancer. / Estandarización de los protocolos de adquisición mediante PET/TC con 18F-Colina en el cáncer de próstata.

AIM: To standardize acquisition protocols for 18F-Choline PET/CT to prevent from urine interference, to determine the best time point for the whole-body study, and to assess whether "dual point" acquisition allows for differentiating malignant vs. benign lesions. METHODS: One hundred consecutive patients with prostate cancer were prospectively studied. Immediately after 18F-Choline injection, a pelvis study was acquired, and a whole-body was subsequently obtained 1 and 2 hours p.i. Mean SUVmax was obtained in regions and for every sequential imaging. Mean analysis (χ2) and SUV percentage change (2/1 hours; 1 hours/0 min) were obtained. Metabolic pattern dynamics were assessed: accumulative vs. clearance. Patient follow-up after therapy and directed classification whenever ethically possible were performed. RESULTS: Fifty-three prostate foci, without disturbing urinary activity was ever found on early images. Accumulative pattern in 42, with percentage increase was: 0 min/1 hour: +16.7% (χ20.94); 1/2 hours: +10,0% (χ2 0.83). Clearance pattern in 11, with percentage decrease: 0 min/1 hour: -21.4% (χ20.91): -7.7% (χ20.85), corresponding in 7 to initial staging and in 4 post-radiotherapy biochemical recurrence. Every infradiaphragmatic uptake (n: 24) showed accumulative pattern, with percentage increase of +9.1% (χ20.97), all of them depicted on early imaging. As for 12 supradiaphragmantic uptake, 8 of them showed clearance pattern with percentage decrease: -13.0% (χ20.95). Accumulative pattern showed in 4 of them with percentage increase +13.0% (χ2 0.96), thus being assessed as invasive/malignant. Every bone uptake (n: 18) showed accumulative pattern, with percentage increase: +17.1% (χ20.95), all of them depicted on 1 hour imaging. CONCLUSIONS: As for prostate assessment is concerned, dual point at 0 min/1 hour proved to be the best procedure. As for supradiaphragmatic lymph-nodes detection, dual point with 1/2 hours performed best. As for infradiaphragmatic and bone involvement, as well as for inconclusive findings, the 2 hour imaging increased our diagnostic confidence.