On the basis of the high and consistent expression of prostatespecific membrane antigen (PSMA) in metastatic prostate cancer (PC), the goal of this study was the development, preclinical evaluation, and first proof-of-concept investigation of a PSMA inhibitor for imaging and therapy (PSMA I&T) for 68 Ga-based PET and 177 Lu-based endoradiotherapeutic treatment in patients with metastatic and castration-resistant disease. Methods: PSMA I&T was synthesized in a combined solid phase and solution chemistry strategy. The PSMA affinity of nat Ga-/ nat Lu-PSMA I&T was determined in a competitive binding assay using LNCaP cells. Internalization kinetics of 68 Ga-and 177 Lu-PSMA I&T were investigated using the same cell line, and biodistribution studies were performed in LNCaP tumor-bearing CD-1 nu/nu mice. Initial human PET imaging studies using 68 Ga-PSMA I&T, as well as endoradiotherapeutic treatment of 2 patients with metastatic PC using 177 Lu-PSMA I&T, were performed. Results: PSMA I&T and its cold gallium and lutetium analog revealed nanomolar affinity toward PSMA. The DOTAGA (1,4,7,10-tetraazacyclododecane-1-(glutamic acid)-4,7,10-triacetic acid) conjugate PSMA I&T allowed fast and high-yield labeling with 68 Ga III and 177 Lu III . Uptake of 68 Ga-/ 177 Lu-PSMA I&T in LNCaP tumor cells is highly efficient and PSMA-specific, as demonstrated by competition studies both in vitro and in vivo. Tumor targeting and tracer kinetics in vivo were fast, with the highest uptake in tumor xenografts and kidneys (both PSMA-specific). First-in-human 68 Ga-PSMA I&T PET imaging allowed high-contrast detection of bone lesions, lymph node, and liver metastases. Endoradiotherapy with 177 Lu-PSMA I&T in 2 patients was found to be effective and safe with no detectable side effects. Conclusion: 68 Ga-PSMA I&T shows potential for high-contrast PET imaging of metastatic PC, whereas its 177 Lu-labeled counterpart exhibits suitable targeting and retention characteristics for successful endoradiotherapeutic treatment. Prospective studies on larger cohorts of patients are warranted and planned.
Certain viral and bacterial infections may contribute to the initiation and progression of atherosclerosis. The aim of this study is to determine whether Helicobacter pylori (HP) seropositivity contributes to conventional atherosclerosis risk factors in the development of an early sign of atherosclerosis: intima-media thickness (IMT) of the carotid artery. Eighty-four patients who had at least two conventional atherosclerosis risk factors and a control group of 50 patients having no risk factors for atherosclerosis were enrolled in the study. None of the patients had ever received HP eradication treatment. HP IgG antibodies were determined by enzyme-linked immunosorbent assay. Carotid artery IMT was measured 1 cm before the carotid bifurcation. Seventy-five percent of the study group was HP seropositive. HP seropositive (n = 64) and seronegative (n = 21) groups were identical in terms of sex distribution, smoking pattern, mean age, hemoglobin, leukocyte, platelet, C-reactive protein, erythrocyte sedimentation rate, glucose, cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, systolic blood pressure and diastolic blood pressure levels. There was no significant difference between the mean carotid IMT of HP seropositive (0.8 ± 0.3 mm) and negative (0.8 ± 0.3 mm) patients in the study group. Similar to the study group, there was no statistically significant difference between mean carotid IMT of HP seropositive (0.56 ± 0.19 mm) and negative patients (0.67 ± 0.13 mm) in the control group (p = 0.2). Future studies concerning virulent strains are needed to determine the probable role of HP in atherosclerosis.
Cryoablation has been used for many years as a surgical ablation technique in the prostate and kidney. However, since the introduction of high-intensity focused ultrasound (HIFU) and robotic surgery for prostate tumours, its popularity in the urologic community has declined. In the early 2000s, innovations in cryoablation technology allowed the use of thinner probes, which were suitable for percutaneous application. As a result, radiologists began using cryoablation, first in the liver, and then in other organs or tissues such as the kidney, lung, breast, pancreas, bone, and soft tissue. In most of these locations, cryoablation has great potential given its inherent advantages, including the use of local anaesthesia, little or no pain during and after the procedure, real-time monitoring of the ablation area on US, CT or MRI, the potential for ablation of large tumours with multiple probes, and the ability to change the shape of the ablation in non-spherical tumours. Yet despite these advantages, the use of percutaneous cryoablation among radiologists appears to be far lower than that of heat-based ablation techniques. The aim of this article is to outline specific aspects of cryoablation and to illustrate its potential clinical applications with case presentations.Key Points• Recent advances have made cryoablation suitable for percutaneous use by radiologists with image guidance.• Cryoablation has distinct advantages over heat-based ablation techniques.• Cryoablation is becoming increasingly popular for lung, breast, kidney, bone, and soft tissue tumours.
The role of imaging studies in the evaluation of patients with sacroiliitis is controversial. We aimed to evaluate the role of nanocolloid and bone scintigraphy in patients with sacroiliitis and to investigate the clinical relevance of imaging findings. Thirty-two patients with clinically sacroiliac disease (nine females, 23 males, aged 22-47 years) underwent scintigraphic and radiographic examinations and all imaging studies were performed within 2 weeks. Twenty-five subjects were also included as a control group (10 females, 15 males, aged 20-51 years) for quantitative analysis of the bone scan. The quantitative analysis was done by using regions of interest drawn over the right and left sacroiliac (SI) joint and sacrum (S) and SI/S ratios were calculated. Abnormal uptake was defined as an uptake higher than the mean +/- 2 SD of the control SI/S values. Bone scintigraphy was performed using a three-phase technique and single photon emission computed tomography (SPECT). Nanocolloid scintigraphy (NS) was performed 1 h later, after administration of 370 MBq 99mTc-nanocolloid, and evaluated visually. Each of the scintigraphic examinations was performed on separate days within the same week. Sensitivity values were 25%, 47%, 69% and 97%, and specificity values were 80%, 90%, 95% and 90% in quantitative bone scanning (QBS), 99mTc-NS, planar and SPECT bone imaging, respectively, when the clinical findings were considered as the 'gold standard'. Our results showed that bone SPECT scanning was more sensitive than planar imaging, but planar imaging was the most specific method. SPECT was also the most associated technique with clinical findings. 99mTc-NS was neither specific nor sensitive enough in the detection of sacroiliitis although it could be helpful for the confirmation of inflammation.
Our results indicate that filling of the stomach with a meal of solid food and liquid before rest acquisition may provide a high target-to-nontarget ratio. This simple modification may reduce the frequency of intestinal activity of Tc-99m-labeled radiopharmaceuticals in myocardial perfusion imaging.
Specific anti-actin and anti-myosin antibodies were shown to react in single and double immunofluorescence sandwich tests with identical sites in non-muscle cells in frozen sections of tissues and in cultured cells. In tissues, both antibodies reacted with liver cell membranes, parts of renal glomeruli, brush borders and peritubular fibrils of renal tubules, brain synaptic junctions, and membranes of lymphoid cells in thymic medulla, lymph nodes and spleen. Both antibodies reacted strongly with long parallel cytoplasmic fibrils in cultured fibroblasts, and with disrupted fibrils in cytochalasin-B treated cells. In neuroblastoma cells both antibodies gave prominent staining of growth cones and microspikes. The observation that the distribution of myosin parallels that of actin in non-muscle cells argues strongly in favour of a functional interaction between the two molecules in the generation of contractile activity in non-muscle cells.
A 30-year-old woman underwent two operations for multinodular goiter and follicular thyroid carcinoma. The residual thyroid tissue was ablated by I-131 therapy. After 7 years of follow-up, Tc-99m MIBI and I-131 scintigraphy were performed, because her serum thyroglobulin level was much higher compared with the control analysis performed in the sixth year. Tc-99m MIBI showed pathologic accumulation, which could be consistent with a local recurrence, whereas the results of I-131 scintigraphy were negative. The locally recurring follicular thyroid carcinoma was resected using a gamma probe and Tc-99m MIBI. The thyroglobulin level decreased to a normal level after surgery. This case shows that the intraoperative use of a gamma probe with Tc-99m MIBI allows localization of recurrent thyroid tissue in the scarred area in patients with increased radionuclide accumulation, and scanning of the affected area using the gamma probe may be helpful in determining whether resection is complete.
This experiment was planned to answer the question of how the elimination of ipsilateral spermatogenetic material, which is necessary for contralateral testicular damage caused by an autoimmune response, affects contralateral testicular blood flow and fertility potential in unilateral spermatic cord torsion (USCT). Thirty-four male and 68 female adult albino rats were divided into three groups. Group 1 rats underwent a control operation, group 2 rats underwent subepididymal orchiectomy to eliminate spermatogenetic material, and group 3 rats underwent USCT after subepididymal orchiectomy. Testicular blood flows of the rats were measured by (133)Xe clearance technique. Additionally, to determine fertility potential, each male rat was housed with two female rats. Numbers of impregnated and delivered rats were recorded. Both mean testicular blood flow and fecundity of group 3 were significantly lower than those of groups 1 and 2. When compared with groups 1 and 2, fertility and mean number of the impregnated rats of group 3 were lower but the differences were not significant. These findings suggest that absence of spermatogenetic material in USCT reduces contralateral blood flow and fertility potential. Therefore, contralateral testicular damage originating from blood flow alterations rather than autoimmune mechanism should be considered to explain fertility problems encountered following USCT.
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