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Purpose: Painful metastatic bone involvement is common in advanced stages of many cancers. Between available radionuclides for bone pain palliation, no consensus has been reached on lutetium ethyle...

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer. However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA-targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 patients with biochemically recurrent prostate cancer. Each subject served as his own control. PET/CT imaging sessions using 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were performed 3-7 d apart, after oral administration of either 12.7 g of MSG or placebo. Data from the 2 sets of images were analyzed by placing regions of interest on lacrimal, parotid, and submandibular glands; left ventricle; liver; spleen; kidneys; bowel; urinary bladder; gluteus muscle; and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the region-of-interest data. Results: In total, 142 pathologic lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in SUVmax corrected for lean body mass (SULmax) on images obtained after MSG administration in the parotids (24% ± 14%, P = 0.001), submandibular glands (35% ± 11%, P < 0.001), and kidneys (23% ± 26%, P = 0.014). Significant decreases were also observed in the lacrimal glands (49% ± 13%, P < 0.001), liver (15% ± 6%, P < 0.001), spleen (28% ± 13%, P = 0.001), and bowel (44% ± 13%, P < 0.001). A mildly lower blood pool SULmean was observed after MSG administration (decrease of 11% ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration than on the placebo studies (SULmax median decrease, 33%; range, -1% to 75%; P < 0.001). No significant adverse events occurred after placebo or MSG administration, and vital signs were stable. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney, and other normal-organ PSMA radiotracer uptake in human subjects, using 18F-DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

Molecular nuclear medicine imaging techniques get a foothold in the diagnosis and treatment response monitoring of various immune-mediated diseases. Several specific radiopharmaceuticals can be used to improve diagnosis, staging, therapy decision-making, and follow-up of infectious, inflammatory, and oncological diseases where immune cells are involved. Several efforts made in the field of nuclear medicine in recent decades have made it possible to evaluate molecules playing a central role in the development of such immune-mediated conditions. The application of molecular imaging techniques may set the stage to assess the expression of the specific molecular targets at the disease site and quantify their presence, giving us a better understanding of the pathogenesis and cellular network of the infective/inflammatory or neoplastic diseases and thus providing an indispensable tool for an individualized therapy decision-making, avoiding side effects and improving therapeutic approaches. In this chapter, we have summarized the immune system, its main building blocks, its innate and adaptive arms, and the role it plays in the development and/or elimination of inflammation, infection, and malignancy. Moreover, the links between the fields of nuclear medicine and immunology, projecting as the procedures for the detection of infection, inflammation, and malignancy, radioimmunoimaging, and radioimmunotherapy, will be discussed.

The 2-fluorodeoxyglucose positron emission tomography/computed tomography (2-[In this retrospective study, 51 metastatic melanoma patients, who had received immunotherapy, were included. Patients with baseline and two follow-up 2-[The 3- and 5-year OS rates were 49% and 43.1%, respectively. On baseline 2-[Metabolic parameters derived from 2-[

European journal of nuclear medicine and molecular imaging 48(12), 4028-4041 (2021). doi:10.1007/s00259-021-05237-y, Published by Springer-Verl., Heidelberg [u.a.]

Noninvasive imaging technique using monoclonal antibodies (mAbs) is a rapidly evolving field, which has entered a new era of development. Recent advancements give rise to a variety of opportunities in the management of various cancers, where the radiolabeled antibodies may be particularly useful in immunospecific phenotypic imaging. While radiolabeled antibodies have been used for 30 years to diagnose and treat cancer, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, now offer new perspectives in immuno-specific phenotype tumor positron-emission tomography (PET) imaging. Both the pretargeting approaches and newly introduced antibody analogs have considerably improved the performances of tumor immunotargeting and renewed the interest in these strategies for both imaging and therapeutic purposes through the provision of companion diagnostics and theranostics to make personalized medicine a reality. In the field of cancer theranostics, we believe that radioimmunoconjugate compounds are likely to play a large part in near future.

Cytokine genes, including interleukin-10 (IL-10), are known to play important roles in the pathogenesis of juvenile idiopathic arthritis (JIA). This study aims to determine whether the IL-10 polymorphisms confer susceptibility to JIA.A meta-analysis was performed on the associations between the IL-10 -1082 G/A, -592 C/A, and -819 C/T polymorphisms and JIA. A total number of 7 studies involving 1,785 patients and 6,142 controls were considered in the meta-analysis.Meta-analysis of the IL-10 -592 C/A and -819 C/T polymorphisms showed no association with JIA in the study participants, or in Caucasian or Middle Eastern participants. Meta-analysis of the IL-10 -1082 A allele in all study participants, Caucasian and Middle Eastern, showed significant associations with RA (overall ORs were 1.17, 1.15, and 1.41, respectively). Meta-analysis of the AA versus GG genotype of the IL-10 -1082 G/A polymorphism revealed significant associations with JIA (OR = 3.66, 95% CI = 1.44-9.29, P = 0.006) in participants from Middle Eastern countries. Additionally, meta-analysis of the GG versus AA+GA genotypes of the IL-10 -1082 G/A polymorphism revealed the GG genotype as the protective factor against JIA in the Middle Eastern subgroup (OR = 0.44, 95% CI = 0.20-0.94, P = 0,04). Moreover, meta-analysis of the IL-10 -1082 A allele in 4 studies on Hardy-Weinberg equilibrium showed a significant association with JIA (OR = 1.17, 95% CI = 1.07-1.28, P = 0.0009). No association was found between the IL-10 (-1082, -819, -592) ACC, ATA, and GCC haplotypes and JIA.These results suggest that the IL-10 -1082 G/A polymorphism confers susceptibility to JIA.

Background The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders, which have been rarely reported to be associated with growth hormone deficiency (GHD). Methods and results A nine-year-old girl with recurrent urinary tract infections, diarrhoea, sinopulmonary infections, and failure to thrive since the age of six months had normal CD3+, CD4+, CD8 + T lymphocytes, and CD19 + B lymphocytes and natural killer (NK) cells, but extremely elevated IgM and significantly decreased IgG and IgA. In view of the patient's short stature, growth hormone evaluation was carried out and growth hormone deficiency established. The patient underwent Ig replacement therapy and received growth hormone therapy in addition to antibiotics and responded well. Furthermore, the patient developed benign cervical lymphadenopathy, as well as elevated erythrocyte sedimentation rate, positive autoantibodies to SSA-Ro, and severely dry eyes, which partially responded to both the punctate occlusion and systemic corticosteroids, at the age of seven years. Sequencing analysis of the exons from activation-induced cytidine deaminase ( AICDA ) gene revealed that the patient was homozygous for a single T to C transversion at position 455 in exon 4, which replaces a Valine with an Alanine. Conclusions To our knowledge, this is a new AICDA mutation, which has not been reported previously in HIGM. The mutation analysis could improve diagnosis of HIGM patients and also elaborating on the spectrum of AICDA mutations.

Traumatic ocular injuries account for a substantial number of emergency department visits annually and represent a significant source of patient disability. A thorough understanding of ocular/optic nerve anatomy and traumatic pathology is fundamental in the accurate and efficient interpretation of emergency neuroradiology. This article will review relevant anatomy, imaging protocols, clinical symptomatology, and key imaging findings associated with the broad spectrum of traumatic ocular and optic nerve pathology.

Introduction and objectives Considering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population. Materials and methods A case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique. Results Analysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility. Conclusion These findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE.

Background Cytokines, including interleukin-1 (IL-1), seem to contribute towards the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL-1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian population. Materials and methods Genomic DNA of 55 Iranian patients with JIA and 140 controls were extracted and typed for IL-1α gene at position −889, IL-1β gene at positions −511 and +3962, IL-1R gene at position Pst-I 1970, and interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. Results The CC genotype of IL-1Ra at Mspa-I 11100 position was found to be more frequent in patients with JIA compared to healthy individuals (P = 0.03), although the CT genotype at the same position was significantly higher in the control group in comparison with patients with JIA (P = 0.02). No significant differences were observed between the two groups of case and control for IL-1α (−889 C/T), IL-1β (−511 C/T and +3962 C/T) and IL-1R (Pst-1 1970 C/T). Conclusion The results of the present investigation suggest that certain IL-1Ra gene variants are associated with individuals’ susceptibility to JIA. Nevertheless, further studies are required to establish the results of the current study.

Purpose Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes in a case control study. Materials and methods The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at −330, rs2069762, and G/T at +166, rs2069763) and IFN-γ (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. Results Results of the analysed data revealed a negative allelic association for JSLE in IL-2 −330/T (P = 0.02), as well as a positive allelic association for IL-2 −330/G (P = 0.02). IL-2 GG genotype (−330) in the patient group was also significantly overrepresented (P

BACKGROUND: Proinfl ammatory cytokines have been known to play a considerable part in the pathomechanisms of chronic heart failure (CHF). Given the importance of proinfl ammatory cytokines in the context of the failing heart, we assessed whether the polymorphisms of interleukin (IL)-1 gene cluster, including IL-1a, IL-1I², and IL-1 receptor antagonist (IL-1RA) and IL-1R gene are predictors of CHF due to ischemic heart disease. METHODS: Forty- three patients with ischemic heart failure were recruited in this study as patients group and compared with 140 healthy unrelated control subjects. Using polymerase chain reaction with sequence-specifi c primers method, the allele and genotype frequency of 5 single nucleotide polymorphisms (SNPs) within the IL- 1a (-889), IL-1I² (-511, +3962), IL-1R (psti 1970), and IL-1RA (mspa1 11100) genes were determined.RESULTS: The frequency of the IL-1I² -511/C allele was signifi cantly higher in the patient group compared to that in the control group (p = 0.031). The IL-1I² (-511) C/C genotype was signifi cantly overrepresented in patients compared to controls (p = 0.022). CONCLUSIONS: Particular allele and genotype in IL-1I² gene were overrepresented in patients with ischemic heart failure, possibly affecting the individual susceptibility to this disease (Tab. 1, Ref. 27). Text in PDF www.elis.sk.

OBJECTIVES The aim of this study is to identify the associations between interleukin 10 (IL-10) and transforming growth factor beta 1 (TGF-β1) gene polymorphisms and individual susceptibility to juvenile idiopathic arthritis (JIA) in a group of Iranian patients. BACKGROUND Cytokine genes, including IL-10 and TGF-β1, are known to play important roles in the pathogenesis of JIA. METHODS Using polymerase chain reaction with sequence-specific primers method, the frequency of alleles, genotypes and haplotypes of IL-10 (positions -1082, -819, -592) and TGF-β1 (codon 10, codon 25) single-nucleotide polymorphisms (SNPs) were investigated in 55 patients with JIA as a case group and compared with 140 healthy unrelated controls. RESULTS The G allele was significantly less frequent at TGF-β1 codon 25 in patients with JIA than in the controls (p < 0.01). The frequency of CT genotype at TGF-β1 codon 10 was found to be higher in healthy individuals in comparison with that in patients group (p = 0.04). We observed no differences in the frequency of alleles, genotypes and haplotypes of IL-10 gene between the groups of patients and controls. CONCLUSIONS Considering the low frequency of existence of TGF-β1 G allele at codon 25 as well as TGF-β1 CT genotype at codon 10 in patients with JIA, it seems that these cytokine gene polymorphisms could play role as the protective factors against JIA.

Purpose. Prognostic significance of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in anal squamous cell carcinoma (SCC) has been evaluated in several studies; however, the results seem to be controversial and no consensus exists about its predictive capability. The current meta-analysis was carried out to comprehensively investigate the prognostic significance of 18F-FDG-PET parameters in patients with anal SCC. Methods. A comprehensive literature search of PubMed/MEDLINE and Scopus databases was performed to retrieve pertinent articles published until August 5th 2018, concerning the prognostic significance of 18F-FDG-PET in patients with anal SCC. No language restriction was used. Several prognostic factors were reported for progression-free survival (PFS) and overall survival (OS) including pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), inguinal nodal uptake, and metabolic response to therapy. Results. Eleven studies (741 patients) were included. The pooled hazard ratio (HR) for the probability of PFS was 5.36 (95% confidence interval (95% CI): 3.12–9.21, p<0.001) for metabolic response to therapy and 1.98 (95% CI: 1.26–3.12, p=0.003) for SUVmax. The pooled HR for the probability of OS was 5.87 (3.02–11.39, p<0.0001) for metabolic response to therapy. On the other hand, the study revealed that the pooled HRs of MTV and inguinal nodal uptake for PFS were 1.56 (95% CI: 0.96–2.53, p=0.072) and 1.79 (95% CI: 1–3.21, p=0.051), respectively. Conclusions. Our findings propose that some 18F-FDG-PET parameters could serve as prognostic indicators in anal SCC, but further larger studies are needed in this setting.

Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease in which both the genetic and environmental factors seem to be involved in the etiopathogenesis of the disease. The aim of this study was to evaluate the association of programmed cell death 1 (PDCD1, also called PD-1) gene polymorphisms with JSLE susceptibility in Iranian population. In this case-control association study, three PDCD1 SNPs, including PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T were genotyped in 50 Iranian patients with JSLE and 202 healthy unrelated controls, using PCR-RFLP method. The PD-1.1 A allele was found to be more frequent in the case group compared with controls (6% vs. 1.5%, p = 0.024). Moreover, the GG genotype was less frequent in cases than in controls (88% vs. 97%, p = 0.021). The other PDCD1 SNPs did not show association. At the haplotypic level, no significant differences was recognized between the two groups of case and control neither for the GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C) nor for the GGC haplotype (PD-1.1 G, PD-1.3 G, PD-1.9 C). Our findings support the influence of the PD1.1 A SNP on the development of JSLE in Iranian population.

Background: As cytokines, including interleukin-10 (IL-10) and transforming growth factor beta 1(TGF-β1) seem to contribute towards the pathogenesis of chronic heart failure (CHF), this study was performed to assess the associations of certain single nucleotide polymorphisms (SNPs) of these genes in a case control study. Methods: This investigation was carried out to determine the frequency of alleles, genotypes and haplotypes of TGF-β1 and IL-10 single-nucleotide polymorphisms (SNPs) in 57 Iranian patients with CHF compared with 140 healthy subjects using polymerase chain reaction with sequence-specific primers method. Results: Results of the analyzed data divulged a negative association for both TGF-β1 GC genotype at codon 25 (P=0.047) and CT genotype at codon 10 (P=0.018) and CHF proneness. Although, TGF-β1 CC genotype at codon 10 was found to be positively associated with CHF (P=0.011). Moreover, the frequency of IL-10 (−1082, -819, -592) ATA haplotype and TGF-β1 (codon 10, codon 25) TG haplotype were significantly lower in the patients group (P=0.004 and P=0.040, respectively), while TGF-β1 (codon 10, codon 25) CG haplotype was overrepresented in patients with CHF (P=0.007). Conclusions: Cytokine gene polymorphisms might affect vulnerability to CHF. Particular genotypes and haplotypes in IL-10 and TGF-β1 genes could render individuals more susceptible to CHF. (www.actabiomedica.it)

Objective: An estrogen-only–producing adrenal tumor is a rare etiology of isosexual precocious puberty (PP) in girls.Methods: We describe a 2.5-year-old girl who presented with signs and symptoms of isosexual PP. In primary laboratory and imaging investigations, serum estradiol level was found to be increased, while follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, cortisol, testosterone, and 17-hydroxyprogesterone levels were shown to be within normal ranges. Abdominopelvic ultrasound and abdominal computed tomography revealed a right-sided adrenal mass, which was initially assumed to be an incidentaloma. Diagnosis of an adrenal cortical tumor was confirmed by tumor resection. Histologic examination revealed the tumor to be a benign adenoma with scattered areas of necrosis.Results: Tumor resection resulted in normalized serum estradiol and diminished clinical signs after 3 weeks. The child received no additional treatment and remains symptom free after 30 months of close observation.Conclusion: With the intent to spread the awareness of adrenocortical tumors as a potentially malignant cause of PP in children, and due to the rarity of an estrogen-producing adrenal mass, we discuss the clinical and biochemical features of our patient and a brief review of the literature.Abbreviations: CT computed tomography;PP precocious puberty

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals’ vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at −174 and +565 positions were assessed. A significant positive association was observed for IL -6 −174 G allele in the patient group (p = 0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p

A 59-year-old man was admitted for fever of unknown origin. Fever was associated with chills. His medical record revealed the history of aortic valve replacement 11 years earlier, as well as enterococcal endocarditis 4 months prior to the current admission. The patient was found to have normal left ventricular size with borderline systolic function, left ventricular hypertrophy, right ventricle at the upper limit of normal size, mild systolic dysfunction and mild transvalvular aortic insufficiency on transthoracic echocardiography; while no vegetations were observed on transesophageal echocardiography. Sequential blood cultures were negative; however, a blood culture sample obtained 5 …

As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value

Cytokines, including interleukin-2 (IL-2) and interferon-gamma (IFN-γ), seem to play a role in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the associations of IL-2 and IFN-γ single nucleotide polymorphisms (SNPs) with susceptibility to JIA in an Iranian population.Genomic DNA of 54 Iranian patients with JIA and 139 healthy unrelated controls were typed for IL-2 (G/T at -330 and +166) as well as IFN-γ gene (A/T at +874), using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls.A significantly higher frequency of the IL-2 -330 GG genotype (p0.01) was found in the JIA patients compared to the controls. However, the GT genotype at the same position was notably lower than in controls (p0.01). Moreover, IL-2 (-330, +166) GT haplotype was more frequent in patients with JIA in comparison with controls. No significant differences was observed between the two groups of case and control for IL-2 (G/T at +166) and IFN-γ (A/T at +874) SNPs.The results of the current study suggest that certain SNPs of IL-2 gene have association with individuals' susceptibility to JIA. However, further investigations are required to confirm the results of this study.

Summary Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disorder of unknown origin. As proinflammatory cytokines are known to contribute towards the pathogenesis of JIA, this case–control study was performed to examine the associations of certain single nucleotide polymorphisms (SNPs) of tumour necrosis factor-α (TNF-α) gene. Fifty-three patients with JIA participated in this study as patients group and compared with 137 healthy unrelated controls. Genotyping was performed for TNF-α gene at positions -308 and -238, using polymerase chain reaction with sequence-specific primers method. Results of the analysed data revealed a significant positive association for TNF-α gene at positions -308 and -238 for A allele in patients group compared with controls (P

Background Recurrent aphthous stomatitis (RAS) is a common disorder with an unclear etiopathogenesis. Involvement of the immune system in the development of this condition is strongly suggested. As the variations in the inflammasome-related NLRP3 gene have been suggested to affect immune system activity, this case–control study was performed to determine whether these genetic variants are associated with RAS. Methods We studied a group of 69 Iranian patients with RAS in comparison with 56 healthy controls. We determined four single nucleotide polymorphisms (SNPs) of NLRP3 and performed association analyses of NLRP3. Genotyping was conducted using the TaqMan method. Results The NLRP3 rs3806265 T allele was significantly more frequent in the patients with RAS than in the healthy controls (P = 0.003). While a significant negative association was found between the C allele at the same position with RAS (P = 0.003), the TT genotype was significantly more frequent at position rs3806265 in NLRP3 in patient group than in the controls (P = 0.002). However, the frequency of CT genotype at the same position was significantly higher in healthy controls than in the case category (P = 0.002). Conclusions Considering the high frequency of the presence of NLRP3 rs3806265 TT genotype in patients with RAS, it seems that this gene polymorphism could affect individual susceptibility to RAS.