[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

Androgen Receptor Imaging in the Management of Hormone-Dependent Cancers with Emphasis on Prostate Cancer.

Prostate cancer is dependent on the action of steroid hormones on the receptors. Endocrine therapy inhibits hormone production or blocks the receptors, thus providing clinical benefit to many, but not all, oncological patients. It is difficult to predict which patient will benefit from endocrine therapy and which will not. Positron Emission Tomography (PET) imaging of androgen receptors (AR) may provide functional information on the likelihood of endocrine therapy response in individual patients. In this article, we review the utility of [18F]FDHT-PET imaging in prostate, breast, and other hormone-dependent cancers expressing AR. The methodologies, development, and new possibilities are discussed as well.

18F-Fluoroethyl-L Tyrosine Positron Emission Tomography Radiomics in the Differentiation of Treatment-Related Changes from Disease Progression in Patients with Glioblastoma.

The follow-up of glioma patients after therapeutic intervention remains a challenging topic, as therapy-related changes can emulate true progression in contrast-enhanced magnetic resonance imaging. 18F-fluoroethyl-tyrosine (18F-FET) is a radiopharmaceutical that accumulates in glioma cells due to an increased expression of L-amino acid transporters and, contrary to gadolinium, does not depend on blood-brain barrier disruption to reach tumoral cells. It has demonstrated a high diagnostic value in the differentiation of tumoral viability and pseudoprogression or any other therapy-related changes, especially when combining traditional visual analysis with modern radiomics. In this review, we aim to cover the potential role of 18F-FET positron emission tomography in everyday clinical practice when applied to the follow-up of patients after the first therapeutical intervention, early response evaluation, and the differential diagnosis between therapy-related changes and progression.

68Ga-DOTA-NT-20.3 Neurotensin Receptor 1 PET Imaging as a Surrogate for Neuroendocrine Differentiation of Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-negative neuroendocrine prostate cancer (PCa) is a subtype of PCa likely to be lethal, with limited clinical diagnostic and therapeutic options. High expression of neurotensin receptor subtype 1 (NTR1) is associated with neuroendocrine differentiation of PCa, which makes NTR1 a potential target for neuroendocrine PCa. In this study, the NTR1-targeted tracer 68Ga-DOTA-NT-20.3 was synthesized, and its affinity to androgen-dependent (LNCap) and androgen-independent (PC3) xenografts was determined. Methods: 68Ga-DOTA-NT-20.3 was labeled using an automated synthesizer module, and its stability, labeling yield, and radiochemical purity were analyzed by radio-high-performance liquid chromatography. Receptor binding affinity was evaluated in NTR1-positive PC3 cells by a competitive binding assay. The biodistribution of 68Ga-DOTA-NT-20.3 in vivo was evaluated in PC3 and LNCap xenografts by small-animal PET imaging. NTR1 expression was identified by immunohistochemistry and immunofluorescence evaluation. Results: 68Ga-DOTA-NT-20.3 was synthesized successfully, with a yield of 88.07% ± 1.26%, radiochemical purity of at least 99%, and favorable stability. The NTR1 affinity (half-maximal inhibitory concentration) for 68Ga-DOTA-NT-20.3 was 7.59 ± 0.41 nM. Small-animal PET/CT of PC3 xenograft animals showed high-contrast images with intense tumor uptake, which revealed specific NTR1 expression. The tumors showed significant radioactivity (4.95 ± 0.67 percentage injected dose per gram of tissue [%ID/g]) at 1 h, which fell to 1.95 ± 0.17 %ID/g (P < 0.01, t = 8.72) after specific blockage by neurotensin. LNCap xenografts had no significant accumulation (0.81 ± 0.06 %ID/g) of 68Ga-DOTA-NT-20.3 at 1 h. In contrast, 68Ga-PSMA-11 was concentrated mainly in LNCap xenografts (8.60 ± 2.11 %ID/g), with no significant uptake in PC3 tumors (0.53 ± 0.05 %ID/g), consistent with the in vitro immunohistochemistry findings. Biodistribution evaluation showed rapid clearance from the blood and main organs (brain, heart, lung, liver, muscle, and bone), with significantly high tumor-to-liver (4.41 ± 0.73) and tumor-to-muscle (12.34 ± 1.32) ratios at 60 min after injection. Conclusion: 68Ga-DOTA-NT-20.3 can be efficiently prepared with a high yield and high radiochemical purity. Its favorable biodistribution and prominent NTR1 affinity make 68Ga-DOTA-NT-20.3 a potential radiopharmaceutical for the detection of PSMA-negative PCa and identification of neuroendocrine differentiation.

Drug tolerability: How much ambiguity can be tolerated? A systematic review of the assessment of tolerability in clinical studies.

AIMS: Drug tolerability refers to the degree to which drugs' overt adverse effects can be tolerated by patients. The tolerability profile is of comparative importance to its efficacy and safety, as it largely determines adherence to treatment and ultimately treatment success or failure. However, the term is frequently used imprecisely, and it is unclear if tolerability is limited to subjective patient-reported symptoms or also covers certain objective signs and findings. The aim of this systematic review was to assess how clinical studies define, evaluate and present drug tolerability. METHODS: The study consisted of a systematic review of clinical studies in PubMed® reporting the term "tolerability". RESULTS: Eighty clinical studies were screened and 56 studies reporting drug tolerability were retained. None of the retained studies defined events encompassed by the term tolerability by making a distinction between safety and tolerability. Twenty-five studies claimed to evaluate tolerability, but none of them described how to evaluate tolerability from the patient perspective. Most studies (54 out of 56) concluded that the treatment was well tolerated, apparently implying favourable safety. However, none of them actually presented tolerability in terms of a contrast between safety and tolerability. CONCLUSIONS: Tolerability is used frequently, albeit incorrectly, to refer to a drug's favourable safety profile. Focused evaluation of drug tolerability (i.e., the patient perspective of adverse drug reactions) should become routine. Presentation in regulatory documents, such as risk management plan summaries, product information and patient leaflets should be a continuation of the process of patient-centred healthcare.

Lack of association between cortical amyloid deposition and glucose metabolism in early stage Alzheimer´s disease patients.

BACKGROUND: Beta amyloid (Aß) causes synaptic dysfunction leading to neuronal death. It is still controversial if the magnitude of Aß deposition correlates with the degree of cognitive impairment. Diagnostic imaging may lead to a better understanding the role of Aß in development of cognitive deficits. The aim of the present study was to investigate if Aß deposition in the corresponding brain region of early stage Alzheimer´s disease (AD) patients, directly correlates to neuronal dysfunction and cognitive impairment indicated by reduced glucose metabolism. PATIENTS AND METHODS: In 30 patients with a clinical phenotype of AD and amyloid positive brain imaging, 2-[18F] fluoro-2-deoxy-d-glucose (FDG) PET/CT was performed. We extracted the average [18F] flutemetamol (Vizamyl) uptake for each of the 16 regions of interest in both hemispheres and computed the standardized uptake value ratio (SUVR) by dividing the Vimazyl intensities by the mean signal of positive and negative control regions. Data were analysed using the R environment for statistical computing and graphics. RESULTS: Any negative correlation between Aß deposition and glucose metabolism in 32 dementia related and corresponding brain regions in AD patients was not found. None of the correlation coefficient values were statistically significant different from zero based on two-sided p- value. CONCLUSIONS: Regional Aß deposition did not correlate negatively with local glucose metabolism in early stage AD patients. Our findings support the role of Aß as a valid biomarker, but does not permit to conclude that Aß is a direct cause for an aberrant brain glucose metabolism and neuronal dysfunction.

18F-FET and 18F-choline PET-CT in patients with MRI-suspected low-grade gliomas: a pilot study.

AIM: To investigate the diagnostic accuracy of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) and fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride (18F-FCH) computed tomography (CT) in patients with primary low-grade gliomas (LGG). METHODS: The study enrolled patients with magnetic resonance imaging (MRI)-suspected LGG. Patients underwent both 18F-FET and 18F-FCH positron emission tomography (PET)-CT. Brain PET-CT was performed according to standard protocol - 20 minutes after intravenous injection of 185 MBq of 18F-FET and 185 MBq of 18F-FCH PET. Surgery and pathohistological diagnosis were performed in the next two weeks. RESULTS: We observed significantly better concordance between tumor histology and 18F-FET PET (weighted Kappa 0.74) compared with both 18F-FCH (weighted Kappa 0.15) and MRI (weighted Kappa 0.00). Tumor histology was significantly associated with 18F-FET (odds ratio 12.87; 95% confidence interval [CI], 0.49-333.70; P=0.013, logistic regression analysis). Receiver operating characteristic curve analysis comparing 18F-FCH (area under the curve [AUC] 0.625, 95% CI 0.298-0.884) and 18F-FET (AUC 0.833, 95% CI 0.499-0.982) showed better diagnostic properties of 18F-FET (AUC difference 0.208, 95% CI -0.145 to 0.562, P=0.248). CONCLUSION: Performing PET-CT in patients with newly diagnosed LGG should be preceded by a selection of an appropriate radiopharmaceutical. 18F-FET seems to be more accurate than 18F-FCH in the LGG diagnosis.

Somatostatin Receptor Subtype Expression in Patients with Acromegaly and Complicated Clinical Course.

Somatostatin analogues are considered to be the first line of treatment in acromegaly. Somatostatin analogues of the first generation mainly target the somatostatin receptor (SSTR) subtype 2 and have been proven efficient in the majority of patients with acromegaly. Pasireotide was the first somatostatin analogue also substantially targeting the SSTR subtype 5. An efficient drug for Cushing's disease tailored to suboptimal-responding patients with acromegaly then became available. We immunohistochemically investigated SSTR subtypes expression in pituitary adenomas from operated acromegaly patients with clinical relapse and a complicated clinical course. Patients received pasireotide in the course of their disease. The predictive value of SSTR subtypes immunhistochemical analysis for the therapeutic response is discussed.

Giant silent corticotrope pituitary adenoma in a patient with complicated clinical course.

Not required for Clinical Vignette.

Safety and tolerability of 68Ga-NT-20.3, a radiopharmaceutical for targeting neurotensin receptors, in patients with pancreatic ductal adenocarcinoma: the first in-human use.

INTRODUCTION: Over the last decades, multiple peptide receptors were recognized as potential diagnostic and therapeutic targets in nuclear medicine. 68Ga-NT-20.3 radiopharmaceutical has been developed for diagnosis of neurotensin receptors. High neurotensin receptor expression has been observed in pancreatic ductal adenocarcinoma as well as various malignancies. Until now, 68Ga-labelled NT ligand was successfully applied in in vitro as well as in animal model. Our study is the first in-human study on safety and tolerability of 68Ga-NT-20.3. METHODS: Subjects were intravenously injected with 2.5 MBq of 68Ga-DOTA-NT-20.3 per kilogramme of body weight, and series of PET images were acquired at 5-25 min, 25-45 min, 45-65 min, and 65-85 min after 68Ga-NT-20.3 injection. Vital parameters are as follows: systolic and diastolic blood pressure (mmHg), heart rate (heart beat/min), respiratory rate (number of breaths/min), ECG, and body temperature (°C) were checked before, immediately after, and 3 h after 68Ga-NT-20.3 injection. The organ-absorbed doses were calculated for the self-dose and cross-dose from each organ region using the OLINDA/EXM version 2.1 software. RESULTS AND CONCLUSION: The results from this small trial demonstrate that PET radiopharmaceutical 68Ga-NT-20.3 is safe and well tolerated.

Effects of Photons Irradiation on 18F-FET and 18F-DOPA Uptake by T98G Glioblastoma Cells.

The differential diagnosis between brain tumors recurrence and early neuroinflammation or late radionecrosis is still an unsolved problem. The new emerging magnetic resonance imaging, computed tomography, and positron emission tomography diagnostic modalities still lack sufficient accuracy. In the last years, a great effort has been made to develop radiotracers able to detect specific altered metabolic pathways or tumor receptor markers. Our research project aims to evaluate irradiation effects on radiopharmaceutical uptake and compare the kinetic of the fluorinate tracers. T98G glioblastoma cells were irradiated at doses of 2, 10, and 20 Gy with photons, and 18F-DOPA and 18F-FET tracer uptake was evaluated. Activity and cell viability at different incubation times were measured. 18F-FET and 18F-DOPA are accumulated via the LAT-1 transporter, but 18F-DOPA is further incorporated, whereas 18F-FET is not metabolized. Therefore, time-activity curves (TACs) tend to plateau with 18F-DOPA and to a rapid washout with 18F-FET. After irradiation, 18F-DOPA TAC resembles the 18F-FET pattern. 18F-DOPA activity peak we observed at 20 min might be fictitious, because earlier time points have not been evaluated, and a higher activity peak before 20 min cannot be excluded. In addition, the activity retained in the irradiated cells remains higher in comparison to the sham ones at all time points investigated. This aspect is similar in the 18F-FET TAC but less evident. Therefore, we can hypothesize the presence of a second intracellular compartment in addition to the amino acidic pool one governed by LAT-1, which could explain the progressive accumulation of 18F-DOPA in unirradiated cells.

Potential use of radiolabelled neurotensin in PET imaging and therapy of patients with pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women. Neurotensin receptors are overexpressed in different malignancies, above all pancreatic cancer. On the other hand, neurotensin receptor expression in inflammation is quite low. This fact can probably solve the most important problem of F-FDG PET imaging - distinguishing malignant and inflammatory processes. The first therapeutic injection of radiolabelled neurotensin in human with pancreatic cancer has been successfully performed. Animal experiments are also very close to the first in human injection of radiolabelled neurotensin for diagnostic purposes. The purpose of this article is to provide an overview of radiolabelled neurotensin analogues that can be used in imaging and therapy in patients with pancreatic ductal adenocarcinoma.

Evidence of 68Ga-DOTA-NT-20.3 Uptake in Pancreatic Adenocarcinoma AsPC-1 Cell Line - in vitro Study.

BACKGROUND: Neurotensin receptors are overexpressed in several cancer types including pancreatic ductal adenocarcinoma. Three NTR subtypes have been cloned: NTR-1, NTR-2 and NTR-3. The most expressed NTR-1 is not present in normal pancreatic tissue and has a low expression in chronic pancreatitis. OBJECTIVE: Objective of this study was to test in vitro affinity of the new 68Ga labelled neurotensin analogue DOTA-NT-20.3 (fragment 6-13, Ac-Lys(DOTA)-Pro-Arg(N-CH3)-Arg-Pro-Tyr-Tle-Leu) on the human pancreatic ductal adenocarcinoma cell line AsPC-1. METHOD: For the preparation of 68Ga-DOTA-NT-20.3, 68GaCl3 solution (eluted from 68Ge/68Ga generator) and 50 µg of precursor (Iason, Graz, Austria) water dissolved were used in an automatic synthesis module. The labeled compound was added to cell culture flask and incubated at 37°C. At various time points after tracer addition up to 80min, cells were recovered, rinsed and counted for radioactivity. Results were expressed as percent binding normalized to 200000 cells and affinity parameters were calculated. RESULTS: Labeling yield was ≥98 %. The molar ratio between labelled and total peptide was about 1/400. AsPC-1 cell line showed rapid uptake of the tracer including surface and internalized binding, tending to a plateau phase 80 min after tracer addition (11%/200.000 cells). The Kd (7.335 pmol) and Bmax (90.52 kBq) value indicated high tracer affinity for AsPC-1cell line especially if compared with the literature data regarding other malignancies (e.g. colonic cancer cell line). Binding sites were 1.09x106 sites per cell. CONCLUSION: New tracer 68Ga-DOTA-NT-20.3 can be a suitable candidate for the clinical use in patients with pancreatic ductal adenocarcinoma.

Uptake of 18F-FET and 18F-FCH in Human Glioblastoma T98G Cell Line after Irradiation with Photons or Carbon Ions.

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. We studied the uptake kinetics of [18F]fluoromethyl-choline (FCH) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) by the T98G human glioblastoma cells from 20 to 120 min after irradiation either with photons at 2-10-20 Gy or with carbon ions at 2 Gy (at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy). We also evaluated the cell death and morphology changes induced by radiation treatment. Both FET and FCH are able to trace tumor behavior in terms of higher uptake for increased doses of radiation treatment, due to the upregulation of cells attempts to repair nonlethal damage. Our data suggest that both FCH and FET could be useful to analyze the metabolic pathways of glioblastoma cells before and after radiotherapy. Physicians will have to consider the different kinetics pathways of uptake concerning the two radiopharmaceuticals.

Imaging of Prostate Cancer Using 18F-Choline PET/Computed Tomography.

18F-fluorocholine (FCH) PET/computed tomography (CT) is a valuable imaging modality in prostate cancer disease. Probably, its main role is restaging of patients with biochemical recurrence after radical prostatectomy or external beam radiotherapy. 18F-FCH PET/CT is strengthening its position in the initial staging, biopsy target definition, radiotherapy planning, and therapy monitoring. Gleason score and prostate-specific antigen value, doubling time, and velocity can influence positivity of 18F-FCH PET/CT. The influence of androgen deprivation therapy on choline uptake is not precisely clarified. Collaboration between nuclear medicine physicians, radiologists, urologists, oncologists, and radiotherapists is crucial to help patients with prostate cancer disease.

Early and Delayed 18F-FCH PET/CT Imaging in Parathyroid Adenomas.

Preoperative localization with Tc-sestaMIBI or ultrasound is a common prerequisite for successful minimally invasive parathyroid adenoma (PA) surgery. SPECT/CT with Tc-sestaMIBI and PET/CT with F-FCH offer the possibility of attenuation correction and coregistration of functional and anatomical images providing more accurate PA localization. F-FCH PET/CT is used predominantly in patients with prostate cancer and is under investigation in PA. We report the case of a 43-year-old man with early FCH uptake in a cystic PA with delayed washout at 60 minutes.

(18)F-fluorodeoxyglucose and (18)F-flumazenil positron emission tomography in patients with refractory epilepsy.

BACKGROUND: Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20-40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). PET/CT can predict surgical outcome in patients with refractory epilepsy. The aim of the article is to review the current role of routinely used tracer 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) as well as non routinely used (18)F-Flumazenil ((18)F-FMZ) tracers PET/CT in patients with refractory epilepsy. CONCLUSIONS: Functional information delivered by PET and the morphologic information delivered by CT or MRI are essential in presurgical evaluation of epilepsy. Nowadays (18)F-FDG PET/CT is a routinely performed imaging modality in localization of the ictal onset zone in patients with refractory epilepsy who are unresponsive to medication therapy. Unfortunately, (18)F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate precisely with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. Benzodiazepine-receptor imaging is a promising alternative in nuclear medicine imaging of epileptogenic focus. The use of (11)C-FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. Therefore, (18)F-FMZ might be established as one of the tracers of choice for patients with refractory epilepsy because of better sensitivity and anatomical resolution.

(18)F-FET and (18)F-FCH uptake in human glioblastoma T98G cell lines.

BACKGROUND: Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. (18)F-methyl-choline ((18)F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The (18)F-ethyl-tyrosine ((18)F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. (18)F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate (18)F-FCH and (18)F-FET uptake by human glioblastoma T98G cells. MATERIAL AND METHODS: Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 10(5) cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for (18)F-FCH and (18)F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 10(5) cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05. RESULTS: A significant uptake of (18)F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of (18)F-FET in comparison to (18)F-FCH was lower by a factor of more than 3, with different kinetic curves.(18)F-FET showed a more rapid initial uptake up to 40 minutes and (18)F-FCH showed a progressive rise reaching a maximum after 90 minutes. CONCLUSIONS: (18)F-FCH and (18)F-FET are candidates for neuro-oncological PET imaging. (18)F-FET could be the most useful oncological PET marker in the presence of reparative changes after therapy, where the higher affinity of (18)F-FCH to inflammatory cells makes it more difficult to discriminate between tumour persistence and non-neoplastic changes. Additional studies on the influence of inflammatory tissue and radionecrotic cellular components on radiopharmaceutical uptake are necessary.

18F-FDG PET/CT in the Initial Assessment and for Follow-up in Patients With Tuberculosis.

PURPOSE: The aim of this retrospective study was to assess the value of 18F-FDG PET/CT in the initial evaluation and follow-up of patients with tuberculosis (TB). PATIENTS AND METHODS: Thirty-five patients (18 men) with pulmonary or extrapulmonary TB were included. Diagnosis of TB was based either on histology or microbiological assessment in 32 patients and was based on typical morphological features of TB in CT and improvement on antimycobacterial medication in 3 patients. Eighty-eight 18F-FDG PET/CT scans were performed at initial assessment and during treatment, on a Siemens Biograph PET/CT. Diagnostic contrast-enhanced CT scans were performed on the 40-slice multidetector CT of the PET/CT scanner. Mean (SD) anti-TB treatment duration was 16.1 (8.9) months. RESULTS: The initial 18F-FDG PET identified 64 affected regions in 34 among 35 patients, whereas CT identified 34 affected organs in 23 patients. Matching image results between PET and CT were observed at first visit in 11 patients (31.4%), with relevant differences in 23 (65.7%). In 1 patient, both modalities remained negative. During follow-up 18F-FDG PET scans, we recorded 15 cases with remission of disease, 16 with residual disease (2 patients with multidrug-resistant infection), and 4 cases with progressive disease or delayed onset of adequate immunological response. In only 3 patients, both modalities, PET and CT, showed completely equivalent results. CONCLUSIONS: Both components of 18F-FDG PET/CT provide complementary information at initial evaluation and during follow-up; however, 18F-FDG showed more abnormal findings than CT. 18F-FDG PET/CT might be useful for the establishment of individualized treatment regimes, but this requires further prospective studies.

The ability of 18F-choline PET/CT to identify local recurrence of prostate cancer.

PURPOSE: To determine when 18F-choline PET/CT can truly identify local recurrence of prostate cancer. METHODS: 1031 patients from 3 European centers underwent (18)F-choline PET/CT (FCH PET/CT) for recurrent disease; 131 subjects (12.7%) showed a positive FCH uptake in the prostatic gland or prostatic fossa. Median age was 72 years (range 48-87 years), and the median PSA level at the time of FCH PET/CT scan was 4.41 ng/mL (0.22-18.13 ng/mL). 45 patients (34.4%) had a Gleason score (GS) >7, and the residual subjects had a GS ≤ 7. The assessment of true or false-positive FCH PET/CT findings was made by magnetic resonance imaging (n = 34) and/or biopsy in 75/131 cases. A χ (2) test and a Z Kolmogorov-Smirnov test were used to assess the correlation between clinical variables (age, PSA, GS, type of therapy) and FCH PET/CT findings. RESULTS: FCH PET/CT resulted truly positive (TP) for recurrent disease in the prostatic gland/fossa in 59/75 patients (79%) and falsely positive (FP) in 16 subjects (21%). The median value of PSA at the time of FCH PET/CT scan was higher in TP as compared to FP, although not statistically significant (4.76 vs. 3.04 ng/mL p > 0.05). Similarly, median age, GS categories, and the type of therapy were similar between the two groups (p > 0.05). However, when matching GS categories and PSA values, we found that the number of patients with TP findings were higher in the case of a PSA > 2 ng/mL, independently from the GS (ranging between 74% and 92%). Conversely, FP rate ranged between 50% and 65% in patients with a PSA ≤ 2 ng/mL, especially in the case of GS ≤ 7, whereas FP was around 25% in those with a GS >7 and PSA > 2 ng/mL. CONCLUSIONS: FCH PET/CT has a limited role in evaluation of prostatic gland/fossa recurrence, due to the physiological biodistribution of the radiopharmaceutical agent. However, in 70-90% of patients with a PSA >2 ng/mL, independently from GS, a focal FCH uptake is compatible with a true local recurrence.