Prediction of clinically significant prostate cancer by [68 Ga]Ga-PSMA-11 PET/CT: a potential tool for selecting patients for active surveillance.

PURPOSE: In our study, our aim was to investigate the role of [68 Ga]Ga-PSMA-11 PET /CT imaging in the diagnosis of clinically significant prostate cancer (csPCa) (ISUP GG 2 and higher) in patients initially diagnosed with ISUP GG 1 and 2 after prostate biopsy. MATERIALS AND METHODS: We retrospectively reviewed 147 patient records in whom [68 Ga]Ga-PSMA-11 PET/CT imaging was performed preoperatively. All patients were initially diagnosed with ISUP GG 1 and 2 PCa by biopsy. Final pathology reports were obtained after radical prostatectomy. The [68 Ga]Ga-PSMA-11 PET/CT images were evaluated to determine the PRIMARY score. Patients' mpMRI-PIRADS scores were also recorded when available and analyzed in correlation with the pathology results. RESULTS: For the 114 patients scored using PRIMARY, 19 out of 37 patients with scores of 1 and 2 (51%) were diagnosed with csPCa. Of the 77 patients with PRIMARY scores between 3 and 5, 64 (83%) had csPCa. Notably, every patient with a PRIMARY score of 5 had csPCa. PRIMARY scoring had a sensitivity of 77% and specificity of 58%, with a positive predictive value of 83%. A moderate correlation was observed between PRIMARY scores and ISUP GG (Rho = 0.54, p < 0.001). In contrast, the PIRADS score displayed a sensitivity and specificity of 86% and 25% respectively, with a positive predictive value of 68%. No substantial correlation was found between PIRADS and ISUP GG. Statistical analysis revealed a significant correlation between PRIMARY and ISUP GG (p < 0.001), but not between PIRADS and ISUP GG (p = 0.281). Comparatively, PRIMARY scoring was significantly more reliable than PIRADS scoring in identifying csPCa. CONCLUSION: [68 Ga]Ga-PSMA-11 PET/CT imaging is promising for distinguishing high-risk prostate cancer patients from those apt for active surveillance, potentially aiding in the identification of csPCa.

Combination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-ß reveals anticancer effect in breast cancer.

BACKGROUND: Platelet derived growth factors (PDGF)-D and the expression of its receptor increase in neoplastic progression of cancer. Co-silencing of growth factor and receptor can be suggested as an important strategy for effective cancer therapy. In the present study, we hypothesized that suppression of PDGF-D signaling pathway with small interfering RNAs (siRNAs) targeting both PDGF-D and PDGF receptor (PDGFR)-ß is a promising strategy for anticancer therapy. METHODS: Chitosan nanoplexes containing dual and single siRNA were prepared at different weight ratios and controlled by gel retardation assay. Characterization, cellular uptake, gene silencing and invasion studies were performed. The effect of nanoplexes on breast tumor growth, PDGF expression and apoptosis was investigated. RESULTS: We have shown that downregulation of PDGF-D and PDGFR-ß with chitosan/siRNA nanoplex formulations reduced proliferation and invasion in breast cancer cells. In the in vivo breast tumor model, it was determined that the intratumoral administration of chitosan/siPDGF-D/siPDGFR-ß nanoplexes markedly decreased the tumor volume and PDGF-D and PDGFR-ß mRNA and protein expression levels and increased apoptosis. CONCLUSIONS: According to the results obtained, we evaluated the effect of PDGF-D and PDGFR-ß on breast tumor development and showed that RNAi-mediated inhibition of this pathway formulated with chitosan nanoplexes can be considered as a new breast cancer therapy strategy.

Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT).

Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

The impact of the extent of the bone involvement on overall survival and toxicity in mCRPC patients receiving [177Lu]Lu-PSMA-617: a WARMTH multicentre study.

INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. METHODS: The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. CONCLUSION: The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

INTRODUCTION: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. MATERIALS AND METHODS: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. RESULTS: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. CONCLUSION: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.

Effect of tadalafil on penile nitric oxide synthase and corporal smooth muscle in rats under dutasteride treatment.

Aim: To investigate the effect of tadalafil in rats administered with daily dutasteride.Methods: Twenty-four Sprague-Dawley male rats were allocated to three groups as control (group C), dutasteride (group D) and dutasteride plus tadalafil (group D + T). After a month of treatment, serum samples were obtained from rats to measure dihydrotestosterone and total testosterone. Nitric oxide (NO) synthase (NOS) immunoreactivity and levels of NOS enzyme isoforms, NO and cyclic guanosine monophosphate (cGMP) were evaluated in the harvested penile tissues. Also, corporal smooth muscle and collagen were examined.Results: Staining intensities of neuronal NOS and endothelial NOS were significantly lower in group D (p < .05). They were similar between group C and group D + T. Immunoreactivity of inducible NOS was observed higher in group D than group C (p = .01) whereas group D + T had the highest iNOS (p<.001). ELISA revealed similar outcomes in terms of NOS enzyme isoform levels. The mean of smooth muscle to collagen ratio was the lowest in group D (p < .001) and it was similar among group C and group D + T (p = .072). Group D had the lowest cGMP and NO levels (p < .05) and they did not differ between group C and group D + T (p>.05). Group D and group D + T had significantly decreased dihydrotestosterone and increased testosterone, compared to group C (p < .001). They were similar between group D and group D + T.Conclusion: Daily treatment with tadalafil improves dutasteride-induced changes in rat penis.

Protective effects of resveratrol on hepatic ischemia reperfusion injury in streptozotocin-induced diabetic rats.

Resveratrol (RSV) is a natural polyphenolic compound having antioxidant effects. This study was designed to investigate the protective effects of resveratrol against oxidative stress in hepatic ischemia-reperfusion (I/R) injury in streptozotocin (STZ)-induced diabetic rats. STZ was injected intraperitonally (i.p.) to 18 Sprague-Dawley albino rats, which were divided into three groups, each having six rats. First group was non-treated diabetic group (D), second diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period (D + I/R), and third diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period and treated with 20 mg/kg/day oral RSV before 30 min I/R injury (D + I/R + RSV). At the end of the experimental period, animals were decapitated, and blood samples were collected to determine tissue tumor necrosis factor-α (TNF-α) levels. Liver and lung tissue samples were obtained for the evaluation of biochemical parameters including malondialdehyde (MDA) and glutathione (GSH) levels and histopathological examinations. Compared to control, I/R injury resulted in decreases in GSH levels and increases in MDA levels. Tissue TNF-α levels were also increased in the D + I/R group compared to D group. Treatment with RSV prevented the alterations on biochemical parameters and histopathological changes induced by I/R. We demonstrate that in diabetic rats, hepatic I/R injury is associated with an augmented inflammatory response and oxidative stress, while RSV pre-treatment significantly decreased these responses. Larger clinical studies are desirable to determine the exact role(s) of RSV on hepatic I/R injury among diabetic subjects.

Ischemic colitis of the colon in streptozotocin-induced diabetic rats.

This study focuses on two inflammatory diseases, viz., "diabetes mellitus (DM)" that causes serious complications such as retinopathy, nephropathy, and neuropathy, and "ischemic colitis" which is evoked by DM. Ischemic colitis originates from the reduction in mesenteric blood flow to the colon with existence of the occlusive or non-occlusive reasons. Our study objective was to provide early diagnostic approach for ischemic colitis in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were divided into four groups: (i) control use of 0.1 M citrate buffer, the solvent of streptozotocin (C), (ii). induced ischemia (I), (iii) rats subjected to 60 mg/kg STZ intraperitoneally to induce type 1 diabetes (D) (48 h after STZ injection, blood glucose levels >200 mg/dl were considered as diabetic), and (iv) diabetic rats subjected to intestinal ischemia (D+I). The third diabetic group (D) was not operated. At the end of the experimental period, rats were sacrificed, C-reactive protein (CRP) and calprotectin levels were measured in the serum and colon tissue specimens. Tissue specimens were also analyzed histologically. We found that serum and colon calprotectin levels were elevated in the D+I group compared to the D and/or I group alone, but relatively calprotectin levels increased in I as compared to C group in colon tissues. CRP levels were significantly increased with ischemic colitis in diabetes, while colon CRP levels were decreased. These results provide evidence for the existence of inflammation in the STZ-induced diabetic rats with ischemic colitis. In conclusion, our measurements of serum calprotectin levels of STZ-induced diabetic rats with ischemic colitis provide a practical approach for an early diagnosis of ischemic colitis. Furthermore, these biochemical analyses correlate well with the histopathologic findings of STZ-induced diabetic rats with ischemic colitis. Future studies would be desirable to further strengthen the role of calprotectin in the early diagnosis of ischemic colitis in diabetics clinical settings.

Red bone marrow dose estimation using several internal dosimetry models for prospective dosimetry-oriented radioiodine therapy.

The aim of the present study was to review the available models developed for calculating red bone marrow dose in radioiodine therapy using clinical data. The study includes 18 patients (12 females and six males) with metastatic differentiated thyroid cancer. Radioiodine tracer of 73 ± 16 MBq 131I was orally administered, followed by blood sampling (2 ml) and whole-body scans (WBSs) done at several time points (2, 6, 24, 48, 72, and ≥ 96 h). Red bone marrow dose was estimated using the OLINDA/EXM 1.0, IDAC-Dose 2.1, and EANM models, the models developed by Shen and co-workers, Keizer and co-workers and Siegel and co-workers, and Traino and co-workers, as well as the single measurement model (SMM). The results were then compared to the standard reference model Revised Sgouros Model (RSM) reported by Wessels and co-workers. The mean dose deviations of the Traino, Siegel, Shen, Keizer, OLINDA/EXM, EANM, SMM, and IDAC-Dose 2.1 models from the RSM were - 17%, - 24%, 6%, - 29%, - 15%, 40%, 48%, and - 8%, respectively. The statistical analysis demonstrated no significant difference between the results obtained with the RSM and with those obtained with the Shen, Traino, OLINDA/EXM, and IDAC-Dose 2.1 models (t test; pvalue > 0.05). However, a significant difference was found between RSM doses and those obtained with the EANM, SMM, and Keizer models (t test; pvalue < 0.05). The correlation between red marrow dose from the SMM and EANM models was modest (R2 = 0.65), while the crossfire dose calculated with the OLINDA/EXM and IDAC-Dose 2.1 models were in good agreement with each other and with the reference model. The findings obtained indicate that most of the dosimetry models can be used for a reliable dosimetry, and the calculated total body doses can be considered as a reliable non-invasive option for a conservative activity planning. In addition, the excellent performance of the IDAC-Dose 2.1 model will be of particular importance for a practical and accurate dosimetry, with the advantages of allowing for the use of realistic advanced phantoms and updated dose fractions, and of providing information about the blood dose contribution to the red bone marrow.

The accuracy of 68Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer.

PURPOSE: To assess the diagnostic accuracy of 68Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging. METHODS: This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Either MRI or CT was used for morphological imaging. PSMA PET/CT was performed and evaluated at a single centre. Sensitivity, specificity and accuracy were calculated for the detection of lymphatic metastases by PSMA PET/CT and morphological imaging. Kappa values were calculated to evaluate the correlation between the numbers of LN metastases detected by PSMA PET/CT and by histopathology. RESULTS: Data on 51 eligible patients are presented. The sensitivity, specificity and accuracy of PSMA PET in detecting LN metastases in the primary setting were 53%, 86% and 76%, and increased to 67%, 88% and 81% in the subgroup with of patients with ≥15 LN removed. Kappa values for the correlation between imaging and pathology were 0.41 for PSMA PET and 0.18 for morphological imaging. CONCLUSIONS: PSMA PET/CT is superior to morphological imaging for the detection of metastatic LNs in patients with primary prostate cancer. Surgical dissection remains the gold standard for precise lymphatic staging.

Tocilizumab's effect on cognitive deficits induced by intracerebroventricular administration of streptozotocin in Alzheimer's model.

Neuroinflammation plays pivotal roles in the pathogenesis of Alzheimer's disease (AD). IL-6 is pleiotropic cytokine which plays significant pathological role in inflammatory diseases and causes prolonged inflammation. Additionally, IL-6 activates microglia cells and enhances the accumulation of amyloid-ß peptides. Moreover, IL-6 signal transduction is mediated by membrane-bound and soluble IL-6 receptors. Tocilizumab which is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody binds to both of these receptors and inhibits IL-6 signaling by this route. The objective was to investigate tocilizumab's potential effects in the treatment of AD. Male Sprague-Dawley rats were divided into three groups: sham (control), streptozotocin (STZ), and tocilizumab-STZ. We used a single dose of intracerebroventricular (ICV) tocilizumab, beginning 1 h prior to injection of STZ for 3 weeks. The rats in STZ and tocilizumab-STZ groups were given ICV-STZ (3 mg/kg). Behavioral parameters were evaluated on days 17-20 and the rats were sacrificed on day-21 to examine histopathological changes. STZ injection caused significant decrease in the mean escape latency in passive avoidance and also declined the performance improvement in Morris water maze tests. Tocilizumab-STZ group significantly improved learning and spatial memory functions by increasing RLT in the passive avoidance and by shortening escape latency in reaching the platform in the Morris water maze. Histopathological changes were examined using hematoxylin and eosin and immunohistochemical (IHC) stainings. IHC analysis revealed that while protein expressions of amyloid-ß (3.5 ± 0.2) and IL-6 (2.9 ± 0.4) showed intense immune-positivity in STZ group, amyloid-ß (1.3 ± 0.1) and IL-6 (1.5 ± 0.2) immunoreactivities were substantially decreased in tocilizumab treatment group. We conclude that tocilizumab treatment attenuated significantly STZ-induced cognitive impairment and histopathological changes. Further studies would be desirable to investigate clinically relevant protective effects of tocilizumab in AD.

Evaluation of radiation safety in (177)Lu-PSMA therapy and development of outpatient treatment protocol.

The aim of this study is to investigate the outpatient treatment protocol and radiation safety of a new-emerging lutetium-177 ((177)Lu) prostate specific membrane antigen (PSMA) therapy. This work analyzed the dose rate of 23 patients treated with 7400 MBq (177)Lu-PSMA at different distances (0, 0.25, 0.50, 1.0 and 2.0 m) and variable time marks (0, 1, 2, 4, 18, 24, 48 and 120 h) after the termination of infusion. Blood samples were withdrawn from 17 patients within the same group at 3, 10, 20, 40, 60 and 90 min and 2, 3, 24 h after termination of infusion. Seven different patients were asked to collect urine for 24 h and a gamma well counter was used for counting samples. Family members were invited to wear an optically stimulated luminescence dosimeter whenever they were in the proximity of the patients up to 4-5 d. The total dose of the medical team including the radiopharmacist, physicist, physician, nurse, and nuclear medicine technologist was estimated by an electronic personnel dosimeter. The finger dose was determined using a ring thermoluminescent dosimeter for the radiopharmacist and nurse. The mean dose rate at 1 m after 4 h and 6 h was 23 ± 6 µSv h(-1) and 15 ± 4 µSv h(-1) respectively. The mean total dose to 23 caregivers was 202.3 ± 42.7 µSv (range: 120-265 µSv). The radiation dose of the nurse and radiopharmacist was 6 and 4 µSv per patient, respectively, whereas the dose of the physicist and physician was 2 µSv. The effective half life of blood distribution and early elimination was 0.4 ± 0.1 h and 5 ± 1 h, respectively. Seven patients excreted a mean of 45% (range: 32%-65%) from the initial activity in 6 h. Our findings demonstrate that (177)Lu-PSMA is a safe treatment modality to be applied as an outpatient protocol, since the dose rate decreases below the determined threshold of <30 µSv h(-1) after approximately 5 h and degrades to 20 µSv h(-1) after 6 h.

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer.

PURPOSE: (177)Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of (177)Lu-labeled PSMA ligand. METHODS: The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected (177)Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. RESULTS: The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. CONCLUSION: Our first results suggested that (177)Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory.

Chard (Beta vulgaris var. cicla) extract improved hyperglycemia-induced oxidative stress and surfactant-associated protein alterations in rat lungs.

CONTEXT: Chard is used as an antidiabetic agent by the diabetic patients in Turkey. OBJECTIVE: The effect of chard extract [Beta vulgaris L. var. cicla (Chenopodiaceae)] on the antioxidant system and the expression of surfactant-associated proteins (SP) in the lungs of hyperglycemic rats were examined. MATERIALS AND METHODS: Hyperglycemia was induced by a single dose of streptozotocin (60 mg/kg) provided intraperitoneally. Fourteen days after the rats were rendered hyperglycemic, the chard (2 g/kg/d), insulin (6 U/kg/d), and chard plus insulin (as mentioned above) were administered to rats for 45 d. On day 60, rats' lungs were removed. Oxidative stress parameters and SP expression were assayed. RESULTS: The lungs of hyperglycemic rats were characterized by the induced lipid and protein oxidation, elevated myeloperoxidase and xanthine oxidase activities, decreased glutathione levels, and reduced tissue factor and antioxidant enzymes activities (catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase). Chard treatment alone and chard treatment combined with insulin were capable of achieving a regression of pulmonary oxidative stress, by inhibiting lipid and protein oxidation, and restoring the antioxidant system of hyperglycemic rats. SP-A expressions were significantly unchanged in all groups, whereas pro-SP-C and SP-D expressions were reduced in hyperglycemic rats. Pro-SP-C and SP-D levels were increased by chard and insulin administrations alone and combined in hyperglycemic rats. DISCUSSION AND CONCLUSION: All treatments have a positive effect on the surfactant and antioxidant systems of the lungs of hyperglycemic rats. The best therapeutic effect was provided by treatment with chard extract alone in the compensation of hyperglycemic symptoms.

FDG and FDG-labelled leucocyte PET/CT in the imaging of prosthetic joint infection.

PURPOSE: The demand for arthroplasty is rapidly growing as a result of the ageing of the population. Although complications such as heterotrophic ossification, fracture and dislocation are relatively rare, differentiating aseptic loosening, the most common complication of arthroplasty from infection, is a major challenge for clinicians. Radionuclide imaging is currently the imaging modality of choice since it is not affected by orthopaedic hardware. Whereas FDG PET/CT imaging has been widely used in periprosthetic infection, it cannot discriminate aseptic from septic inflammation. In this study we aimed to evaluate the role of FDG PET/CT and FDG-labelled leucocyte PET/CT in the diagnosis of periprosthetic infection. METHODS: Of 54 patients with painful joint arthroplasty who were imaged by FDG PET/CT for diagnosis of periprosthetic infection examined, 46 (36 women, 10 men; mean age 61.04 ± 12.2 years, range 32-89 years) with 54 painful joint prostheses (19 hip, 35 knee) with grade 2 (above liver uptake) FDG accumulation on FDG PET/CT were included in the study and these 46 patients also underwent FDG-labelled leucocyte PET/CT. Final diagnoses were made by histopathological-microbiological culture or clinical follow-up. RESULTS: The final diagnosis showed infection in 15 (28%) and aseptic loosening in 39 (72%) of the 54 prostheses. FDG PET/CT was found to have a positive predictive value of 28% (15/54). Since patients with no FDG uptake on FDG PET/CT were excluded from the study, the sensitivity, specificity, negative predictive value and accuracy could not be calculated. The sensitivity, specificity, and positive and negative predictive values of FDG-labelled leucocyte PET/CT were 93.3% (14/15), 97.4% (38/39), 93.3% and 97.4%, respectively. CONCLUSION: Since FDG is not specific to infection, the specificity of FDG PET/CT was very low. FDG-labelled leucocyte PET/CT with its high specificity may be a useful method and better than labelled leucocyte scintigraphy in periprosthetic infection imaging.

Revision of the Histopathological Examination Following 68Ga-DOTA-FAPI-04 PET/CT of a Breast Tumor Diagnosed as Invasive Ductal Carcinomatosis.

Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions. Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root. Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established. The benefit of FAPI-PET/CT on NETs has been previously investigated. Further prospective studies are required to establish the role of FAPI-PET/CT in NET management.

Von Hippel Lindau disease with metastatic pancreatic neuroendocrine tumor causing ectopic Cushing's syndrome.

We present a 39-year-old woman who was previously diagnosed with Von Hippel Lindau Disease (VHLD). She had surgery and radiotherapy for cranial hemangioblastoma (HA) 11 years ago and had unilateral adrenalectomy for pheochromocytoma in another hospital 6 month prior to her admission to our center. Moon face, buffalo hump, central obesity, progressive weight gain and menstrual irregularities persisted after adrenalectomy. Her laboratory results were consistent with ectopic Cushing's syndrome (ECS). A pancreatic solid mass with a nodule on the left lung were revealed upon computed tomography. In addition, Gallium-68 Somatostatin Receptor PET confirmed the pancreatic involvement and demonstrated additional lesions on the left lung and in the aortocaval lymphatic system on the right side, suggesting metastatic pancreatic neuroendocrine tumor (PNET). Peptide receptor radionuclide therapy (PRRT) with [177Lutetium-DOTA0,Tyr3] octreotate was performed on the patient, with no side effects observed. She was discharged from the hospital 10 days after the first cycle.