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.

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors.

Objectives: This study aimed to evaluate the stability, safety, and efficacy of alpha-targeted therapy with [225Ac]Ac-DOTATATE in patients with grade 1/2 metastatic neuroendocrine tumors (NETs). Methods: This retrospective cohort included patients (n=11) with metastatic NETs from different primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic NETs, paraganglioma, and unknown primary site) treated with [225Ac]Ac-DOTATATE with a mean activity of 8.2±0.6 MBq (range: 7.5-10.0 MBq) at our institution between November 2019 and March 2022. The in vivo and in vitro stability of [225Ac]Ac-DOTATATE was calculated. The safety profile was evaluated according to the CTCAE-v5.0. Treatment efficacy was evaluated according to [68Ga] Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) images and the RECIST 1.1 criteria. Results: Patients had 73% (n=8) lymph node metastases, 91% (n=10) liver metastases, 36% (n=4) lung metastases, and 73% (n=8) bone metastases. All but one patient was refractory to treatment with [177Lu]Lu-DOTATATE. [225Ac]Ac-DOTATATE was stable for at least 5 h in vitro (in saline) and 3 h in vivo (urine and blood samples). Grade 2 renal toxicity and grade 2 hematotoxicity were observed in one patient. No grade 3-4 toxicities were reported. According to post-treatment [68Ga]Ga-DOTATATE PET/CT (n=9), 11% (n=1) had progressive disease, 44.4% (n=4) had stable disease, and 44.4% (n=4) had a partial response. The disease control rate was 89% (n=8). The median progression-free survival estimated according to Kaplan-Meier analysis was 12 months. Conclusion: The preliminary results of this study suggest that [225Ac]Ac-DOTATATE is stable, safe, and effective for treating advanced and [177Lu] Lu-DOTATATE-refractory NETs. However, prospective studies are needed to determine the impact of treatment on overall survival and to uncover potential side effects.

Differentiated Thyroid Cancer in Children and Adolescents: Clinicopathological Characteristics of 32 Patients Followed up in our Pediatric Endocrinology Unit.

Objectives: This study aims to investigate the clinical and pathological features of patients with differentiated thyroid cancer (DTC) treated at our tertiary care institution. Methods: Thirty-two children and adolescents followed up with the diagnosis of DTC between 2001 and 2017 were enrolled. We classified patients with DTC into two groups as below and above 10 years of age, and compared their clinical and pathological features. Results: The mean age at presentation was 11.2±4 years. The female/male ratio was 7 (28:4). The diagnosis was papillary thyroid cancer (PTC) in 90.6% (n=29). The frequencies of lymph node and pulmonary metastases were 53.1% and 21.8%, respectively. The groups were comparable in terms of gender, initial clinical signs and tumor histopathology. The mean tumor size was greater in the younger age group (p=0.008). However, there was no difference between the two groups in terms of lymph node and pulmonary metastases. The pathological parameters associated with tumor aggressiveness were also similar between the groups, except lymphovascular invasion. Lymphovascular invasion was more frequent in the younger age group (p=0.01). Patients with lymph node and pulmonary metastases were more likely to have extrathyroidal extension and lymphovascular invasion. Conclusion: PTC was the most common type of DTC and presented with considerable rates of lymph node and pulmonary metastases. Tumor size was greater and lymphovascular invasion was more common in younger patients. Overall prognosis was favorable despite high rates of lymph node and pulmonary metastases.

Clinical Experience with [225Ac]Ac-PSMA Treatment in Patients with [177Lu]Lu-PSMA-Refractory Metastatic Castration-Resistant Prostate Cancer.

For patients with advanced-stage metastatic castration-resistant prostate cancer (mCRPC) who do not respond to [177Lu]Lu-PSMA therapy, there are limited treatment options. Clinical results obtained with [225Ac]Ac-PSMA are promising. We retrospectively analyzed the outcomes of patients treated with [225Ac]Ac-PSMA between December 2018 and October 2022. Methods: We evaluated the treatment results of 23 patients (mean age, 70.3 ± 8.8 y) with mCRPC who were refractory to treatment with [177Lu]Lu-PSMA (2-9 cycles). The safety profile was assessed according to Common Technology Criteria for Adverse Events version 5.0. Treatment efficacy was assessed using prostate-specific membrane antigen PET progression criteria and prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 2 criteria after the first cycle of [225Ac]Ac-PSMA treatment. Results: All patients received androgen-deprivation therapy, whereas 22 (96%) and 19 (83%) patients received chemotherapy and second-generation antiandrogen therapy, respectively. One patient received 4 cycles, 2 received 3 cycles, 8 received 2 cycles, and 12 received 1 cycle of [225Ac]Ac-PSMA. The median interval between cycles was 13 wk (range, 8-28 wk). [225Ac]Ac-PSMA was administered with a mean activity of 7.6 MBq (range, 6.2-10.0 MBq) in each cycle. Patients were at an advanced stage of disease, and tumor burden was very high. Although the best PSA response was observed in 5 patients (26%) after [225Ac]Ac-PSMA treatment, there was at least some level of decline in PSA observed in 11 patients (58%; n = 19). Treatment response was assessed in patients who underwent [68Ga]Ga-PSMA PET/CT imaging. After the first cycle of treatment (n = 18), 50% of patients (n = 9) showed disease progression according to prostate-specific membrane antigen PET progression criteria, and the disease control rate was calculated to be 50%. Median progression-free survival was 3.1 mo, and median overall survival was 7.7 mo. Grade 3 hematologic toxicity occurred in 1 patient, and grade 3 nephrotoxicity was observed in another patient. Parotid SUVmax decreased by 33%, although all patients complained of dry mouth before treatment. Conclusion: We observed that [225Ac]Ac-PSMA therapy was safe and showed potential even in cases with advanced-stage mCRPC in which all other treatment options were completed.

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 relationship between tumor mean standard uptake value (SUVmax) in preoperative PET/computed tomography and prognostic risk groups in endometrial cancer.

OBJECTIVE: Our aim in this study was to determine the relationship between tumor mean standard uptake value (SUVmax) value in preoperative PET/computed tomography (CT) and prognostic risk groups in cases with endometrial cancer. METHODS: A total of 368 patients operated on for endometrial cancer were evaluated in the study. The SUVmax value of endometrial primary tumor of the patients screened within 30 days of operation, was compared with prognostic parameters and risk groups. P value <0.05 was considered significant for all tests. RESULTS: A statistically significant relationship was found between the mean SUVmax value and risk groups ( P < 0.001), grade ( P < 0.001), stage ( P < 0.001), myometrial invasion of the tumor ( P < 0.001), cervical involvement ( P = 0.002), lymphovascular space invasion (LVSI) ( P < 0.001), lymph node metastasis ( P < 0.001), tumor size ( P < 0.001), lymph node involvement in PET/CT ( P < 0.001). There was no significant relationship found between the histologic type of tumor and the mean SUVmax value ( P = 0.113). Cutoff SUVmax value for endometrial cancer tumor tissue, which will be used to determine the possible lymph node metastasis, was accepted as 19 as a result of the ROC analysis. The risk of lymph node metastasis was found 4.74 times (confidence interval, 2.510-8.977) higher in patients with SUVmax value above cutoff 19 ( P < 0.001). Considering risk groups, it was observed that patients with mean SUVmax value above 19 were in intermediate-high and high risk group, 2.3 times more than those in low and intermediate risk group ( P < 0.001). As a result of logistic regression analysis, in determining intermediate-high and high-risk groups, histological type ( P < 0.001), myometrial invasion ( P = 0.003), cervical invasion (CI) ( P < 0.001), grade ( P = 0.018) and SUVmax value ( P = 0.028) had statistically significant importance. CONCLUSION: The higher the mean SUVmax value in the endometrial cancer tumor tissue in preoperative PET/CT in patients with endometrial cancer, the higher the risk group of the patients.

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.

Almost Complete Response with a Single Administration 225Ac-DOTATATE in a Patient with a Metastatic Neuroendocrine Tumor of Unknown Primary.

Neuroendocrine tumors (NETs) are being seen increasingly frequently, and the only known curative treatment method is surgical resection. Peptide receptor radionuclide therapy (PRRT) is a treatment option that the most contributes to progression-free survival and overall survival in metastatic cases.ß-emitting radionuclides are traditionally used for PRRT. Nowadays, alpha particle-emitting radionuclides are being developed, with advantages in terms of very high energy and a short path length, which should theoretically show higher efficacy. In this case; in a patient with NET diagnosis who had multiple (>50) lesions in the abdomen, almost all the lesions disappeared with a single dose application. This paper aims to present a case in which we observed the efficacy of 225Ac-DOTATATE treatment, which is an alpha treatment.

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.

Evaluation of F-18 DOPA PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: comparison with GA-68 DOTA-TATE PET/CT.

OBJECTIVE: PET imaging with F-18 DOPA (FDOPA) and Ga-68 DOTATATE (TATE) shows the most promising results to detect medullary thyroid cancer (MTC) recurrence. We performed this comparative study to detect the site of recurrent or metastatic disease in MTC patients with elevated serum calcitonin (Ctn) and/or carcinoembryonic antigen (CEA) levels. METHODS: We studied 46 MTC patients (25 women, 21 men) with elevated Ctn and/or CEA levels during follow-up who had both FDOPA and TATE PET/CT scans for re-staging purposes. RESULTS: FDOPA PET imaging yielded an overall sensitivity of 86.8%, specificity of 100%, PPV of 100%, NPV of 61.5%, and accuracy of 89.1%, while TATE PET scan had the same values as 84.2%, 87.5%, 96.9%, 53.8%, and 84.6%, respectively, and there was no statistically significant difference between the two modalities with the exception of the specificity value that was higher for FDOPA imaging. In a subgroup of patients with overt Ctn or CEA elevation, sensitivity of FDOPA increased significantly, whereas TATE sensitivity did not change. FDOPA PET imaging was significantly superior in detecting liver and regional lymph node (LN) metastases, while TATE PET scan was significantly better in the skeletal metastases. Early FDOPA demonstrated 11 invisible lesions on late FDOPA. CONCLUSION: Both FDOPA and TATE PET/CT imaging are useful to localize recurrences in MTC patients. While TATE imaging is superior to reveal skeletal disease, FDOPA seems better in liver and regional LN metastases; therefore, the two modalities appear complementary in monitoring MTC patients with elevated serum Ctn and/or CEA levels.

Consensus on molecular imaging and theranostics in neuroendocrine neoplasms.

Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.

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.

Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study.

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug.

The Role of 68GA-PSMA PET/CT Scan In Patients with Prostate Adenocarcinoma who Underwent Radical Prostatectomy.

PURPOSE: To determine whether a 68Ga-PSMA PET/CT scan evaluation before radical prostatectomy (RP) is an effective imaging modality for clinical local and lymph node (LN) staging compared with the pathological results. MATERIALS AND METHODS: We performed a preoperative 68Ga-PSMA PET/CT scan in 51 patients with prostate cancer (PCa), who were scheduled for an RP operation between January 2014 and June 2016 in our clinic. The correlation between the RP pathology and the results of the 68Ga-PSMA PET/CT scan was investigated. RESULTS: When the 68Ga-PSMA PET/CT scan results were evaluated according to the risk groups, intraprostatic activity was found in 5 of 12 patients (41.7%) in the low-risk group, 15 of 19 patients in the intermediate risk group (78.9%), and 90% patients in the high-risk group. The 68Ga-PSMA PET/CT scan sensitivity, specificity, positive and negative predictive values and accuracy were calculated as 58.2%, 75.3%, 84.4%, 44%, and 63%, respectively for intraprostatic tumor localization; 68.4%, 75%, 61.9%, 80%, and %72.6%, respectively for extracapsular extension; 63.6%, 92.3%, 70%, 90%, and 86%, respectively for seminal vesicle involvement; 50%, 100%, 100%, 88%, and 89.3%, respectively for LN metastasis. CONCLUSION: The 68Ga-PSMA PET/CT scan accurately demonstrates intraprostatic tumor localization in high-risk group and presence of seminal vesicle involvement, which can help to accurately detect the target lesion before prostate biopsy. In addition, with its high sensitivity and specificity values, 68Ga-PSMA PET/CT is a valuable imaging method for the assessment of LN metastasis in intermediate- and high-risk groups and also provides accurate nodal staging before RP.

Synthesis, molecular modeling, in vivo study and anticancer activity against prostate cancer of (+) (S)-naproxen derivatives.

In this study, (S)-naproxen thiosemicarbazides (3a-d), 1,2,4-triazoles (4a-c), triazole-thioether hybride compounds (5a-p) were synthesized and their structures (3a, 3d, 4a and 5a-p) were confirmed by FT-IR, 1H NMR,13C NMR, HR-Mass spectra and elemental analysis. These compounds are designed to inhibit methionine amino peptidase-2 (MetAP2) enzyme in prostate cancer. These compounds (3d, 5a-p) evaluated against androgen-independent prostate adenocarcinoma (PC-3, DU-145) and androgen-dependent prostate adenocarcinoma (LNCaP) cell lines by using MTS method. Compounds 5a, 5b, 5d and 5e showed 14.2, 5.8, 10.8 and 8.4 µM anticancer activity against PC-3 cell lines, compounds 5e, 5g and 5n presented anticancer activity against DU-145 cell lines 18.8, 12.25 and 10.2 µM, and compounds 5g, 5m and 5n exhibited anticancer activity against LNCaP cell lines 12.25, 22.76 and 2.21 µM, respectively. Consequently, of these results, compounds 5e and 5n showed the highest activities against androgen dependent and independent prostate cancer cell lines, so these compounds could be potent small molecules against prostate cancer. Furthermore, mitogen-activated protein kinase (MAPK) pathway activation, AKT (protein kinase B) phosphorylation and androgen receptor activation of compound 5n (SGK636) were investigated in LNCaP cells by using Western blot method. Compound 5n (SGK636) was also tested against mRNA expression analysis of the Bax, Bcl-2, Caspase 3, Caspase 9 by using real-time PCR analysis. Compound 5n was given to nude male mice with cancer in comparison to the control group. Compound 5n was found to reverse the malignant phenotype in the nude male mice, whereas the prostate cancer progressed in the control group. Analysis of some blood parameters in the study showed that they were within the normal values with respect to the control. The blood values of the animals treated according to the control group also exhibited compliance with the blood limit values. Molecular docking and dynamics simulation of compound 5n binding to Methionine Aminopeptidase 2 (MetAP2) enzyme rationalized its potential activity. In addition, inhibition assay MetAP2 enzyme of compound 5n was evaluated. Taken together, we suggest compound 5n to be a potential candidate for prostate cancer therapy.

Therapy-related chronic myeloid leukemia in a patient receiving peptide receptor radionuclide therapy for pancreatic neuroendocrine tumor.

BACKGROUND: Therapy-related leukemia is a well-recognized clinical syndrome. Peptide receptor radionuclide therapy (PRRT) is a modern therapeutic approach using radionuclide combined with somatostatin analog peptide for inoperable or metastatic neuroendocrine tumors. AIMS: Hematologic toxicities including late-onset myeloid neoplasms have been reported after PRRT; however, therapy-related chronic myeloid leukemia (TR-CML) following PRRT is a relatively rare entity. METHODS: We present a 64-year-old male who received PRRT for pancreas neuroendocrine tumor and then developed TR-CML 60 months after the initiation of PRRT. The patient responded well to imatinib therapy. RESULTS: Patients with TR-CML generally have similar tyrosine kinase inhibitor responses and outcomes when compared to de novo cases. CONCLUSIONS: The physicians should be aware of the short- and long-term hematologic toxicities of PRRT including TR-CML, and careful monitoring is mandatory in this group of patients.

A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches.

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth.

Interobserver and intraobserver agreement on prostate-specific membrane antigen PET/CT images according to the miTNM and PSMA-RADS criteria.

AIM: In this study, we aimed to measure interobserver and intraobserver agreement in Ga-68-prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) image interpretation. In addition, the limitations of these criteria and levels of personal confidence reported by the readers when reporting the findings were determined. The effects of interpersonal differences on clinical decisions were also investigated. METHODS: PSMA PET images from 133 cases were reported independently by four different readers at different times according to the molecular imaging TNM (miTNM) and PSMA-reporting and data system (RADS) templates. RESULTS: There was substantial interobserver agreement for overall positivity, miT, miN and miM staging (Fleiss' κ = 0.65, 0.625, 0.731, and 0.779). Substantial agreement levels were observed in reporting of seminal vesicle invasion, the number of lymph node stations with metastasis, total number of intraprostatic areas containing tumors, and lymph node metastasis staging (Fleiss' κ = 0.622 and 0.779). The highest variation was seen in the reporting of intraprostatic distribution: In International Society of Urological Pathology (ISUP) grade group 1, moderate agreement was observed, and it was seen that the agreement level for the T staging increased with an increasing ISUP group in the staging group (Fleiss' κ = 0.531 vs. 0.655). There was near-perfect interobserver agreement in the reporting of five-point PSMA-RADS scoring [intraclass correlation coefficient (ICC) κ = 0.904; 95% CI, 0.865-0.934]. Disagreement according to miTNM staging had a major effect on clinical management in only 9% (n = 12) of the patients. CONCLUSION: PSMA PET has a lower interobserver variability and higher reproducibility than other imaging methods used for imaging of prostate cancer do, including CT, MRI, and bone scintigraphy. The miTNM template provides a reporting format that is highly reproducible and has a high level of agreement among readers, but the prostatic template needs development. In contrast, the PSMA-RADS system leads to slightly increased interobserver reporting differences and reduces personal confidence, but at the same time, it still exhibits almost-perfect agreement in terms of scoring.