Diagnostic value of asymmetric striatal D<Subscript>2</Subscript> receptor upregulation in Parkinson’s disease: an [<Superscript>123</Superscript>I]IBZM and [<Superscript>123</Superscript>I]FP-CIT SPECT study

Introduction Striatal postsynaptic D₂ receptors in Parkinson’s disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D₂ binding is found contralateral to the most affected side in PD, and whether this upregulation can be used as a diagnostic tool. Methods Cross-sectional survey was undertaken of 81 patients with clinically asymmetric PD, without antiparkinsonian drugs and with a disease duration of ≤5 years and 26 age-matched controls. Striatal D₂ binding was assessed with [¹²³I]IBZM SPECT, and severity of the presynaptic dopaminergic lesion with [¹²³I]FP-CIT SPECT. Results The mean striato-occipital ratio of [¹²³I]IBZM binding was significantly higher in PD patients (1.56 ±0.09) than in controls (1.53 ±0.06). In PD patients, higher values were found contralateral to the clinically most affected side (1.57 ±0.09 vs 1.55 ±0.10 ipsilaterally), suggesting D₂ receptor upregulation, and the reverse was seen using [¹²³I]FP-CIT SPECT. However, on an individual basis only 56% of PD patients showed this upregulation. Conclusion Our study confirms asymmetric D₂ receptor upregulation in PD. However, the sensitivity of contralateral higher striatal [¹²³I]IBZM binding is only 56%. Therefore, the presence of contralateral higher striatal IBZM binding has insufficient diagnostic accuracy for PD, and PD cannot be excluded in patients with parkinsonism and no contralateral upregulation of D₂ receptors, assessed with [¹²³I]IBZM SPECT.     

A novel computer-assisted image analysis of [<Superscript>123</Superscript>I]β-CIT SPECT images improves the diagnostic accuracy of parkinsonian disorders

Purpose  

The purpose of this study was to develop an observer-independent algorithm for the correct classification of dopamine transporter SPECT images as Parkinson’s disease (PD), multiple system atrophy parkinson variant (MSA-P), progressive supranuclear palsy (PSP) or normal.     

PET imaging of α<Subscript>7</Subscript> nicotinic acetylcholine receptors: a comparative study of [<Superscript>18</Superscript>F]ASEM and [<Superscript>18</Superscript>F]DBT-10 in nonhuman primates,and further evaluation of [<Superscript>18</Superscript>F]ASEM in humans

Purpose

The α₇ nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α₇ nAChRs PET radioligands, [¹⁸F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [¹⁸F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [¹⁸F]ASEM in humans.

Methods

PET scans with high specific activity [¹⁸F]ASEM or [¹⁸F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [¹⁸F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [¹⁸F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [¹⁸F]ASEM distribution volume (V _T). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V _T was assessed.

Results

In the rhesus monkey brain [¹⁸F]ASEM and [¹⁸F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [¹⁸F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [¹⁸F]ASEM V _T. [¹⁸F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [¹⁸F]ASEM V _T in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V _T values ranging from 19.6?±?2.5 mL/cm³ in cerebellum to 25.9?±?2.9 mL/cm³ in thalamus. Test-retest variability of V _T was 11.7?±?9.8%.

Conclusions

These results confirm [¹⁸F]ASEM as a suitable radiotracer for the imaging and quantification of α₇ nAChRs in humans.

     

Effect of cyclosporin A administration on the biodistribution and multipinhole μSPECT imaging of [<Superscript>123</Superscript>I]R91150 in rodent brain

Purpose  P-glycoprotein (Pgp) is an efflux protein found amongst other locations in the blood–brain barrier. It is important to investigate the effect of Pgp modulation on clinically used brain tracers, because brain uptake of the tracer can be altered by blocking of the Pgp efflux transporter. The function of Pgp can be blocked with cyclosporin A. Methods  We investigated the effect of cyclosporin A administration on the biodistribution of [¹²³I]R91150 in rodents, and the effect of Pgp blocking on the quality of multipinhole μSPECT imaging with [¹²³I]R91150. The influence of increasing doses of cyclosporin A on the brain uptake of [¹²³I]R91150 was investigated in NMRI mice. A biodistribution study with [¹²³I]R91150 was performed in male Sprague-Dawley rats pretreated with cyclosporin A and not pretreated. Brain uptake of [¹²³I]R91150 after cyclosporin A injection was compared to the brain uptake in untreated animals, and a displacement study with ketanserin was performed in both groups. A multipinhole μSPECT brain imaging study was also performed using a Milabs U-SPECT-II camera in male Sprague-Dawley rats. To exclude the effect of possible metabolites, a metabolite study was also performed. Results  At the highest cyclosporin A dose (50 mg/kg), a sevenfold increase in brain radioactivity concentration was observed in NMRI mice. Also, a dose-response relationship was established between the dose of cyclosporin A and the brain uptake of [¹²³I]R91150 in mice. Compared to the control group, a five-fold increase in [¹²³I]R91150 radioactivity concentration was observed in the brain of Sprague-Dawley rats after cyclosporin A treatment (50 mg/kg). Radioactivity concentration in the frontal cortex increased from 0.24±0.0092 to 1.58±0.097% injected dose per gram of tissue after treatment with cyclosporin A (at the 1-h time-point). Blood radioactivity concentrations did not increase to the same extent. The cortical activity was displaced by administration of ketanserin. A metabolite study confirmed that there was no increased metabolism of [¹²³I]R91150 due to cyclosporin A. The visual quality of multipinhole μSPECT images with [¹²³I]R91150 in Sprague-Dawley rats improved markedly after cyclosporin A pretreatment. Conclusion  From the results obtained in the biodistribution studies, it can be concluded that [¹²³I]R91150 is a substrate for Pgp in rodents. A relationship between the administered dose of cyclosporin A and the increase in [¹²³I]R91150 brain radioactivity concentration was established. The overall quality of our multipinhole μSPECT images with [¹²³I]R91150 in rats improved markedly after pretreatment of the animals with cyclosporin A.     

Early [<Superscript>18</Superscript>F]florbetaben and [<Superscript>11</Superscript>C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer’s disease

Purpose

[¹⁸F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [¹¹C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [¹⁸F]FDG uptake. Uptake data for ¹⁸F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [¹⁸F]FBB in the diagnosis of Alzhimers disease (AD).

Methods

This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [¹¹C]PiB (11 patients) or [¹⁸F]FBB (11 patients) in routine clinical practice. Images were acquired 1 – 9 min after administration of both tracers and 40 – 70 min and 90 – 110 min after administration of [¹¹C]PiB and [¹⁸F]FBB, respectively. The patients also underwent [¹⁸F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated.

Results

Regional visual scores of early Aβ tracer and [¹⁸F]FDG PET images were significantly correlated (Spearman’s ρ?=?0.780, P?<?0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [¹⁸F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [¹⁸F]FDG data (r?=?0.779, P?<?0.001), but there were no differences between [¹⁸F]FBB and [¹¹C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [¹⁸F]FDG PET images were correlated with MMSE scores (ρ?=?0.458, P?=?0.032, and ρ?=?0.456, P?=?0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [¹⁸F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison.

Conclusion

Early [¹⁸F]FBB and [¹¹C]PiB PET brain images are similar to [¹⁸F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [¹⁸F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.

     

Serotonin transporter binding with [<Superscript>123</Superscript>I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Purpose  The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods  We included 49 depressed outpatients (mean±SD 42.3 ± 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [¹²³I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP_ND) in the midbrain and diencephalon with cerebellar binding as a reference. Results  In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p = 0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p = 0.002) and an additional smoking×gender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter. Conclusion  Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.     

[<Superscript>18</Superscript>F]FDG PET monitoring of tumour response to chemotherapy: does [<Superscript>18</Superscript>F]FDG uptake correlate with the viable tumour cell fraction?

Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [(18)F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [(18)F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5 x 10(6) Daudi cells. When the tumour measured 15-20 mm, Endoxan was given intravenously. At different time points [1-15 days (d1-d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [(18)F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [(18)F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [(18)F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [(18)F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [(18)F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells.     

Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [<Superscript>123</Superscript>I]β-CIT SPECT

Purpose  

We characterized the progression of dopamine transporter (DAT) decline in the striatum and extrastriatal regions including the midbrain and pons of patients with the Parkinson variant of multiple system atrophy (MSA-P) and compared longitudinally collected SPECT results with those in a cohort of patients with Parkinson's disease (PD).     

Extraction,selection and comparison of features for an effective automated computer-aided diagnosis of Parkinson’s disease based on [<Superscript>123</Superscript>I]FP-CIT SPECT images

Purpose

This work aimed to assess the potential of a set of features extracted from [¹²³I]FP-CIT SPECT brain images to be used in the computer-aided “in vivo” confirmation of dopaminergic degeneration and therefore to assist clinical decision to diagnose Parkinson’s disease.

Methods

Seven features were computed from each brain hemisphere: five standard features related to uptake ratios on the striatum and two features related to the estimated volume and length of the striatal region with normal uptake. The features were tested on a dataset of 652 [¹²³I]FP-CIT SPECT brain images from the Parkinson’s Progression Markers Initiative. The discrimination capacities of each feature individually and groups of features were assessed using three different machine learning techniques: support vector machines (SVM), k-nearest neighbors and logistic regression.

Results

Cross-validation results based on SVM have shown that, individually, the features that generated the highest accuracies were the length of the striatal region (96.5%), the putaminal binding potential (95.4%) and the striatal binding potential (93.9%) with no statistically significant differences among them. The highest classification accuracy was obtained using all features simultaneously (accuracy 97.9%, sensitivity 98% and specificity 97.6%). Generally, slightly better results were obtained using the SVM with no statistically significant difference to the other classifiers for most of the features.

Conclusions

The length of the striatal region uptake is clinically useful and highly valuable to confirm dopaminergic degeneration “in vivo” as an aid to the diagnosis of Parkinson’s disease. It compares fairly well to the standard uptake ratio-based features, reaching, at least, similar accuracies and is easier to obtain automatically. Thus, we propose its day to day clinical use, jointly with the uptake ratio-based features, in the computer-aided diagnosis of dopaminergic degeneration in Parkinson’s disease.

     

<Superscript>123</Superscript>I–Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice

Purpose

Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice.

Methods

We synthesized ¹²³I–oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the ¹²³I–oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of ¹²³I–oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of ¹²³I–oxLDL in serum was assessed by radio-HPLC.

Results

The cellular uptakes of ¹²³I–oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of ¹²³I–oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min post-injection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining ¹²³I–oxLDL or its metabolites in the blood.

Conclusion

¹²³I–OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.

     

Synthesis and basic evaluation of 7α-(3-[<Superscript>18</Superscript>F]fluoropropyl)-testosterone and 7α-(3-[<Superscript>18</Superscript>F]fluoropropyl)-dihydrotestosterone

Objective

7α-Substituted androgen derivatives may have the potential to visualize androgen receptors with positron emission tomography. In the present study, we synthesized fluoropropyl derivatives of 7α-(3-[¹⁸F]fluoropropyl)-testosterone ([¹⁸F]7) and 7α-(3-[¹⁸F]fluoropropyl)-dihydrotestosterone ([¹⁸F]15), and characterized their in vitro binding, in vivo biodistribution, and performed blocking studies in mature androgen deprived male rats.

Methods

We synthesized [¹⁸F]7 and [¹⁸F]15. In vitro binding to recombinant rat AR ligand binding domain protein was determined using a competitive radiometric ligand-binding assay with the high-affinity synthetic androgen [17α-methyl-³H]-methyltrienolone ([³H]R1881). In vivo biodistribution was performed in mature male rats treated with diethylstilbestrol (chemical castration). A blocking study was performed by co-administration of dihydrotestosterone (36 µg/animal).

Results

7α-(3-Fluoropropyl)-testosterone (7) and 7α-(3-fluoropropyl)-dihydrotestosterone (15) showed competitive binding to recombinant rat AR ligand binding domain protein. The IC₅₀ value of 15 (13.0 ± 3.3 nM) was higher than 7 (47.8 ± 10.0 nM). In contrast to the AR binding affinity, the ventral prostate uptake of [¹⁸F]7 and [¹⁸F]15 at 2 h post-injection was similar (0.07 % injected dose/g of tissue). A blocking study indicated that specific binding of [¹⁸F]15 is observed in the ventral prostate. [¹⁸F]7 and [¹⁸F]15 showed moderate levels of bone uptake, which indicates moderate metabolic de-fluorination in rodents.

Conclusion

[¹⁸F]15 is better than [¹⁸F]7 in terms of radiochemical yield, in vitro binding affinity, prostate specific binding and stability against in vivo metabolic de-fluorination. However, the net uptake level of [¹⁸F]15 in prostate might be insufficient for in vivo visualization. Although [¹⁸F]7 and [¹⁸F]15 improved in vivo stability against de-fluorination, other basic characterization data in rodents were not superior to the current standard tracer 16β-[¹⁸F]fluoro-5α-dihydrotestosterone. It is also revealed that the shorter side chain length of 7α-[¹⁸F]fluoromethyl-dihydrotestosterone is superior to the longer three carbon chain in [¹⁸F]15, in terms of net prostate uptake and in vivo metabolic stability.

     

Longitudinal Decline of Striatal Subregional [<Superscript>18</Superscript>F]FP-CIT Uptake in Parkinson’s Disease

Purpose

Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson’s disease (PD) progression and monitoring drug effects. We investigated the longitudinal decline characteristics of striatal [¹⁸F]FP-CIT uptake in PD.

Methods

We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [¹⁸F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs.

Results

Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen.

Conclusions

The longitudinal decline of striatal [¹⁸F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.

     

Molecular imaging of σ receptors: synthesis and evaluation of the potent σ<Subscript>1</Subscript> selective radioligand [<Superscript>18</Superscript>F]fluspidine

Purpose  

Neuroimaging of σ₁ receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable ¹⁸F-labelled PET radioligands for that purpose.     

Do androgens control the uptake of <Superscript>18</Superscript>F-FDG, <Superscript>11</Superscript>C-choline and <Superscript>11</Superscript>C-acetate in human prostate cancer cell lines?

Purpose  

The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines—reflecting different stages of the disease—on ¹⁸F-fluorodeoxyglucose (FDG), ¹¹C-choline and ¹¹C-acetate uptake.     

Dopamine transporter SPECT using fast kinetic ligands: <Superscript>123</Superscript>I-FP-β-CIT versus <Superscript>99m</Superscript>Tc-TRODAT-1

A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, ¹²³I-FP--CIT (FP) and ^99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0±1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1–2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinsons disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (–8.8%/year, =–0.41, P=0.025) and the putamen/caudate ratio (–7.4%/year, =–0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.     

<Superscript>125</Superscript>I brachytherapy in younger prostate cancer patients

Purpose

To evaluate local recurrence in younger men treated with low-dose-rate (LDR) ¹²⁵I brachytherapy (BT) for localized prostate cancer.

Patients and methods

A total of 192 patients (≤65-years-old) were treated with LDR ¹²⁵I-BT ± hormone therapy. Local failure was defined as any prostate-specific antigen (PSA) rise leading to salvage treatment or biochemical failure according to the Phoenix definition. A bounce was defined as a rise in the nadir of ≥0.2?ng/mL followed by spontaneous return. Proportions were compared using Fisher’s exact tests; continuous variables using the unpaired t-test or its non-parametric equivalent. Cox proportional hazards models were applied for multivariable survival analysis.

Results

Median follow-up was 66 months. The 5?year local recurrence-free survival was 96.1%. Biopsy-proven local recurrence developed in 13 patients, 4 had a Phoenix-defined recurrence at the last follow-up. Androgen deprivation therapy was started in 1 patient without proven recurrence. Univariable risk factors for local recurrence were: at least 50% positive biopsies, intermediate risk, treatment with neoadjuvant hormone therapy, low preimplantation volume receiving 100% of the prescribed dose, and no bounce development. Hormone-naïve patients not attaining a PSA value <0.5?ng/mL during follow-up also had a higher risk of local recurrences. Cox regression demonstrated that the variables “at least 50% positive biopsies” and “bounce” significantly impacted local failure (hazard ratio, HR 1.02 and 11.59, respectively). A bounce developed in 70 patients (36%). Younger patients and those treated with a lower activity per volume had a higher chance of developing a bounce in the Cox model (HR 0.99 and 0.04, respectively).

Conclusion

For younger men, LDR BT is a valid primary curative treatment option in low-risk and is to consider in intermediate-risk localized prostate cancer.

     

Test–retest stability of cerebral A<Subscript>1</Subscript> adenosine receptor quantification using [<Superscript>18</Superscript>F]CPFPX and PET

PURPOSE: The goal of the present study was to evaluate the reproducibility of cerebral A1 adenosine receptor (A1AR) quantification using [18F]CPFPX and PET in a test-retest design. METHODS: Eleven healthy volunteers were studied twice. Eight brain regions ranging from high to low receptor binding were examined. [18F]CPFPX was injected as a bolus with subsequent infusion over 120 min. Various outcome parameters were compared based on either metabolite-corrected venous blood sampling [e.g. apparent equilibrium total distribution volume (DVt')] or a reference region [ratio of specific to non-specific distribution volume (BP2)]. RESULTS: Test-retest variability was low in the outcome measure BP2 (on average 5.9%) and moderate in DVt' (on average 13.2%). Regarding reproducibility, the outcome parameter BP2 showed an intra-class correlation coefficient (ICC) of 0.94 +/- 0.1. For DVt' the between-subject coefficient of variation (%CV) was similar to the within-subject %CV (around 10%), resulting in a poor ICC of 0.06 +/- 0.2. CONCLUSION: Our results suggest that quantification of [18F]CPFPX imaging is reproducible and reliable for PET studies of the cerebral A1AR. Among the outcome parameters the non-invasive measures were of superior test-retest stability over the invasive.