Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a therapeutic modality which has been used for the treatment of cancers, including brain and head and neck tumors. For effective treatment via BNCT, efficient and selective delivery of a high boron dose to cancer cells is needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer imaging and drug delivery. In this study, we conjugated boronic acid or carborane functional groups to a well-established PSMA inhibitor scaffold to deliver boron to prostate cancer cells and prostate tumor xenograft models. Eight boron-containing PSMA inhibitors were synthesized. All of these compounds showed a strong binding affinity to PSMA in a competition radioligand binding assay (IC50 from 555.7 to 20.3 nM). Three selected compounds 1a, 1d, and 1f were administered to mice, and their in vivo blocking of 68Ga-PSMA-11 uptake was demonstrated through a positron emission tomography (PET) imaging and biodistribution experiment. Biodistribution analysis demonstrated boron uptake of 4-7 µg/g in 22Rv1 prostate xenograft tumors and similar tumor/muscle ratios compared to the ratio for the most commonly used BNCT compound, 4-borono-l-phenylalanine (BPA). Taken together, these data suggest a potential role for PSMA targeted BNCT agents in prostate cancer therapy following suitable optimization.

Neurological structures and mediators of pain sensation in anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) tears is a devastating injury and one of the most common knee injuries experienced by athletes in the United States. Although patients reach maximal subjective improvement by one-year following ACL reconstruction, many patients often experience moderate to severe post-operative pain. Opioids, intra-articular injections, and regional anesthesia have been previously implemented to mediate post-operative pain. However, chronic opioid usage has become an epidemic in the United States. Alternative analgesic modalities, such as nerve blocks, have been implemented in clinical practice to provide adequate pain relief and minimize opioid usage. Periarticular injections targeted towards local neurological structures performed concomitantly with nerve blocks provides superior pain relief and satisfaction than isolated nerve blocks. Therefore, it is imperative for physicians to understand local neurological anatomy around the knee joint in order to provide adequate analgesia while minimizing opioid consumption. This purpose of this investigation is to summarize (1) neurogenic origins of pain generators and mediators in sites affected by ACL reconstruction and autograft harvest sites and (2) analgesia utilized in ACL reconstruction.

The effects of serotonin1A receptor on female mice body weight and food intake are associated with the differential expression of hypothalamic neuropeptides and the GABAA receptor.

Both common eating disorders anorexia nervosa and bulimia nervosa are characteristically diseases of women. To characterize the role of the 5-HT1A receptor (5-HT1A-R) in these eating disorders in females, we investigated the effect of saline or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) treatment on feeding behavior and body weight in adult WT female mice and in adult 5-HT1A-R knockout (KO) female mice. Our results showed that KO female mice have lower food intake and body weight than WT female mice. Administration of 8-OH-DPAT decreased food intake but not body weight in WT female mice. Furthermore, qRT-PCR was employed to analyze the expression levels of neuropeptides, γ-aminobutyric acid A receptor subunit ß (GABAA ß subunits) and glutamic acid decarboxylase in the hypothalamic area. The results showed the difference in food intake between WT and KO mice was accompanied by differential expression of POMC, CART and GABAA ß2, and the difference in body weight between WT and KO mice was associated with significantly different expression levels of CART and GABAA ß2. As such, our data provide new insight into the role of 5-HT1A-R in both feeding behavior and the associated expression of neuropeptides and the GABAA receptor.