Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects

Effect of an extract of Centella asiatica on the biodistribution of sodium pertechnetate (Na^99mTcO₄) and on the fixation of radioactivity on blood constituents

This study evaluates the effects of an acute treatment with a Centella asiatica (CA) extract on the biodistribution of the radiopharmaceutical Na99mTcO4 and on the fixation of technetium-99m on blood constituents. Wistar rats were treated with CA extract and, 1 hour after, Na99mTcO4 was administered; organs/tissues were withdrawn and weighted. The radioactivity was counted to calculate the percentage of activity per gram (%ATI/g). Also, blood samples were withdrawn, plasma (P), blood cells (BC), insoluble fraction (IF) and soluble fractions of P and BC were isolated and the radioactivity was counted to calculate the percentage of activity (%ATI). Data indicated that the acute treatment with CA extract changed significantly (p99mTcO4 and the fixation of the technetium-99m on blood constituents in an acute treatment

Nuclear medicine procedures and the evaluation of male sexual organs: a short review

Sexuality consists of three aspects that are interrelated and inseparable, biological, physiological and social. The biological aspect considers the individual's capability to give and to receive pleasure. In consequence, it covers the functionality of the sexual organs and the physiology of human sexual response cycle. Diagnostic imaging modalities, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) have been used to evaluate clinical disorders of the male reproductive system. PET and SPECT procedures basically involve the administration of a radiopharmaceutical that has a higher uptake in a specific tumor or tissue. The aim of this brief review is to present some radiopharmaceuticals that have been used in the clinical evaluation of the male sexual organs (testes, prostate, seminal vesicles, penis) related with male sexuality. This information could be useful in better understanding the male sexual response cycle, as well as the sexual disorders, when considering the male sexual organs and the pelvic floor. Moreover, the findings obtained with PET and SPECT imaging could help to evaluate the efficacy of clinical results of therapeutic procedures. In conclusion, the knowledge from these images could aid in better understanding the physiology of the different organs related with sexuality. Furthermore, they could be important tools to evaluate the physiological integrity of the involved organs, to improve clinical strategies and to accompany the patients under treatment

The role of epigenetics in renal ageing

An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects

Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer

Peer reviewe

Selection of aptamers with high affinity and high specificity against C595, an anti-MUC1 IgG3 monoclonal antibody, for antibody targeting

Targeting of antibodies has found a number of applications in assays, anti-idiotypic therapies and vaccine design with a number of anti-idiotypic Abs generated and used in clinical applications, and some currently in clinical trials. Meanwhile, aptamers are a novel and particularly interesting targeting modality, with a unique ability to bind to a variety of targets. Aptamers offer unique benefits compared to other targeting agents, due to their high affinity and selectivity, relatively small size and in vitro synthesis, making them attractive alternatives to Abs and peptides. Aptamers have already been selected against a number of Abs for various applications. We now present a novel methodology for the selection of aptamers against Abs, which minimises the number of steps used and results in molecules that bind to the target Ab with high affinity and specificity. We have used the well-characterised anti-MUC1 monoclonal Ab C595 as an exemplar for raising aptamers against Abs. The methodology is based on the adsorption of the Ab to the surface of a PCR tube and the performance of SELEX selections in the PCR tube, based on elution steps resulting from the denaturation of the Ab on the first PCR amplification cycle. After 10 rounds of selection and amplification, selected aptamers have been characterised using a number of techniques, including fluorescence quenching, ELISA and competition ELISA procedures and a FRET type assay. Aptamers were found to bind their target Ab with a higher affinity than its natural antigenic peptide, as observed in fluorescent quenching and FRET experiments. Furthermore, they were able to displace the antigens from the antibody binding pocket in competition assays. This methodology offers the possibility of rapidly selecting aptamers for antibody targeting that could be used as diagnostic, imaging or therapeutic agents, or as recognition units in immunoassays, and can be potentially useful in raising aptamers against other protein targets

Detection, Monitoring and Treatment of Cancer

This invention relates to compounds which are useful in the detection, monitoring and treatment of cancer and to the detection, monitoring and treatment of cancer using such compounds