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.

Mapping Aldehyde Dehydrogenase 1A1 Activity using an [18 F]Substrate-Based Approach.

Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of aldehydes to carboxylic acids. Elevated ALDH expression in human cancers is linked to metastases and poor overall survival. Despite ALDH being a poor prognostic factor, the non-invasive assessment of ALDH activity in vivo has not been possible due to a lack of sensitive and translational imaging agents. Presented in this report are the synthesis and biological evaluation of ALDH1A1-selective chemical probes composed of an aromatic aldehyde derived from N,N-diethylamino benzaldehyde (DEAB) linked to a fluorinated pyridine ring either via an amide or amine linkage. Of the focused library of compounds evaluated, N-ethyl-6-(fluoro)-N-(4-formylbenzyl)nicotinamide 4 b was found to have excellent affinity and isozyme selectivity for ALDH1A1 in vitro. Following 18 F-fluorination, [18 F]4 b was taken up by colorectal tumor cells and trapped through the conversion to its 18 F-labeled carboxylate product under the action of ALDH. In vivo positron emission tomography revealed high uptake of [18 F]4 b in the lungs and liver, with radioactivity cleared through the urinary tract. Oxidation of [18 F]4 b, however, was observed in vivo, which may limit the tissue penetration of this first-in-class radiotracer.

Variability in the amount of fluorine-18 fluorodeoxyglucose excreted in urine measured from oncology patients during PET/computed tomography imaging.

The objectives of this work were to estimate the amount of fluorine-18 fluorodeoxyglucose (F-FDG) excreted (AFE) in the patient urine during the uptake phase as percentage of the injected activity and to examine the effect of blood glucose levels (BGL) on the excreted amount and whether it varies among men and women using statistical analysis methods. Radiation dose rates were measured at 1 m from 50 patients, 24 men and 26 women, before and after the first void using a calibrated ionization chamber. The F-FDG was injected in the patients using a calibrated automatic dose injection system. Statistical analysis using hypothesis testing was carried out. Patients with BGL above 5 mmol/l had a higher AFE of 12.3% in comparison with 8.3% of the patients with BGL below 5 mmol/l. A statistically nonsignificant correlation (r=0.183, P<0.249) between AFE and BGL was found; a nonsignificant difference was found in the AFE measured among the male and female patients. The AFE measured was 12±6%, with a range of (2-30%). There was a wide variation in the first void time of 39±8 min, with a range of (17-68) min. A simple noninvasive measurement method is presented that enabled the estimation of the amount of F-FDG excreted from the patient during voiding. Statistical analysis concluded that the amount of F-FDG excreted does not depend on sex, but is perhaps influenced by BGL.

Phase I, first-in-human study of BMS747158, a novel 18F-labeled tracer for myocardial perfusion PET: dosimetry, biodistribution, safety, and imaging characteristics after a single injection at rest.

UNLABELLED: (18)F-labeled BMS747158 is a novel myocardial perfusion imaging tracer that targets mitochondrial complex 1. The objectives of this phase I study were to evaluate radiation dosimetry, biodistribution, human safety, tolerability, and early elimination of (18)F activity in urine after injection of a single dose of the tracer at rest in healthy subjects. METHODS: Thirteen healthy subjects were injected with 170-244 MBq (4.6-6.6 mCi) of BMS747158 intravenously. Dynamic PET was obtained over the heart for 10 min, followed by sequential whole-body imaging for 5 h. Blood samples and urinary excretion were collected for up to 8 h. Heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. The residence times were determined from multiexponential regression of organ region-of-interest data normalized by injected dose. Absorbed dose estimates for all target organs were determined using MIRD schema with OLINDA/EXM software. RESULTS: The organ receiving the largest mean absorbed dose was the kidneys at 0.066 mSv/MBq (0.24 rem/mCi), followed by the heart wall at 0.048 mSv/MBq (0.18 rem/mCi). The mean effective dose was 0.019 mSv/MBq (0.072 rem/mCi). The heart exhibited high and sustained retention of BMS747158 from the earliest images through approximately 5 h after injection. There were no drug-related adverse events, and the tracer was well tolerated in all subjects. Mean urinary excretion was 4.83 percentage injected dose (range, 0.64-12.41 percentage injected dose). CONCLUSION: These preliminary data suggest that (18)F-labeled BMS747158 appears to be well tolerated and has a unique potential for myocardial perfusion PET.

[18F-FDG PET/CT with retrograde filling of the urinary bladder in the assessment of malignant pelvic disease]. / PET-TAC con (18)F-FDG tras llenado retrógrado vesical en el estudio de patología pélvica maligna.

AIM: To assess the role of PET/CT with retrograde filling of urinary bladder (RFUB) in the assessment of pelvic malignancy in patients with urothelial or gynecological tumors. MATERIAL AND METHODS: A retrospective longitudinal analysis based on 62 studies belonging to 52 patients was performed. All of them had a history of pelvic malignancy (29 urothelial and 23 gynecological) and 42 had undergone previous treatments. All patients underwent a standard PET/CT protocol. Inclusion criteria were radiological alterations in pelvic organs or increased urinary activity of (18)F-FDG that hindered evaluation of the pelvic structures. Pathological pelvic locations were assessed as the additional value of PET/CT with RFUB. The pathologic lesions were histologically or clinically evaluated with a minimum follow-up of 12 months. RESULTS: Pelvic malignancy was confirmed in 33 cases, 16 of which were of urothelial origin. A total of 35/62 studies showed a pathologic PET/CT in pelvis, 4 of them were false positive and 2 false negative. In 19 cases, malignancy was detected in the bladder wall, 16 of which were true positive. No false negative was detected. Regarding standard imaging acquisition, RFUB helped to confirm or rule out bladder and/or gynecological disease in 54 cases. CONCLUSION: Retrograde bladder filling is a highly recommended technique in the assessment of malignant pelvic disease, especially of bladder origin.

Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine.

The whole-body distribution of O-(2-[(18)F]fluoroethyl)- l-tyrosine (FET) was studied in seven patients with brain tumours by positron emission tomography (PET). Based on the IMEDOSE and MIRDOSE procedures, radiation absorbed doses were estimated from whole-body PET scans acquired approximately 70 and 200 min after i.v. injection of 400 MBq FET. After injection of FET, the peak of radioactivity in the blood was observed after 1.5 min, and a plateau of nearly constant radioactivity was reached at 20 min. The whole-body distribution of FET showed the highest activities in the urinary tract. All other organs exhibited only moderate FET uptake (SUV

Evaluation of 18F-FA-4 and 11C-pipzA-4 as radioligands for the in vivo evaluation of the high-affinity choline uptake system.

UNLABELLED: 4,4'-Bis-1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl-biphenyl (A-4), a tertiary amine analog of hemicholinium-3 (HC-3), is an inhibitor of the sodium-dependent high-affinity choline uptake (HACU) system. We have evaluated 4-[1-hydroxy-2-(4-(18)F-fluoromethylpiperidin-1-yl)ethyl]-4'-[1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl]biphenyl ((18)F-FA-4) and 4-[1-hydroxy-2-(4-(11)C-methylpiperazin-1-yl)ethyl]-4'-[1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl]biphenyl ((11)C-pipzA-4), an (18)F- and a (11)C-labeled derivative of A-4 as potential in vivo tracers for the HACU system. METHODS: The biodistribution of both compounds was determined in mice, and the intracerebral distribution was visualized by ex vivo and in vitro autoradiography. The in vitro affinity of the compounds was determined by a displacement study with (3)H-HC-3 on mice brain slices. RESULTS: In mice, both tracers show a high and persistent brain uptake. In vitro autoradiography shows binding to the striatum, whereas ex vivo autoradiography shows homogeneous binding throughout the brain. FA-4 and pipzA-4 inhibited the (3)H-HC-3 binding with a 50% inhibitory concentration of 57 nmol/L and 320 nmol/L, respectively. CONCLUSION: The evaluated compounds have affinity for HACU and show high uptake in the brain. In vitro binding of the compounds to the striatum cannot be inhibited by the presence of HC-3, whereas binding of HC-3 was inhibited by the presence of both FA-4 and pipzA-4, suggesting allosteric binding.

Imaging and quantitation of the hypoxic cell fraction of viable tumor in an animal model of intracerebral high grade glioma using [18F]fluoromisonidazole (FMISO).

We have demonstrated that FMISO uptake is significantly higher in tumor tissue in the C6 intracerebral glioma rat model compared to normal brain, and that there is persisting hypoxia in gliomas independent of tumor size. FMISO uptake was observed homogeneously throughout viable glioma tissue in tumor sizes ranging from 2mm to almost 1cm. Quantitation of uptake of FMISO showed a tumor/brain ratio of 1.9 and a tumor/blood ratio of 2.6 at 2 hours post injection.