The theranostic use of fibroblast activation protein inhibitors (FAPIs) is a novel approach in oncology. Sarcomas are a heterogenous group of rare malignant tumors. Prognosis remains poor in advanced/metastatic disease due to limited therapeutic options. Sarcoma frequently demonstrate high expression of fibroblast activation protein alpha on the tumor cells themselves, in contrast to other solid tumors, where it is mainly expressed on cancer-associated fibroblasts. Consequently, high in vivo uptake of FAPI in PET is observed in sarcoma. Moreover, retrospective case reports and series demonstrated feasibility of FAPI radioligand therapy with signs of tumor response.

Paralytic shellfish poisoning (PSP) events occur regularly along the Mediterranean and Atlantic coast of Morocco, and have been responsible for several severe cases of human intoxication. Along the southern Atlantic coast of Morocco, aquaculture and intensive artisanal fishing practices have recently been particularly heavily impacted, and toxic species have been observed in increasing intensity and frequency. In the 1990\'s a regulatory monitoring program was established for the coastal waters off Morocco by the National Institute of Fisheries Research (INRH), to reduce the risk of intoxication with biotoxins. The regulatory monitoring is conducted weekly and includes toxic phytoplankton enumeration and identification, as well as saxitoxin (STX) analysis in seafood using the mouse bioassay (MBA). Animal testing remains the most widely used screening method for PSP toxin detection, yet its use is being reconsidered for animal-related ethical issues, as well as for practical considerations. To be able to better evaluate alternatives to animal testing, the performance of a nuclear-based radioligand-receptor binding assay (RBA) for paralytic shellfish toxins was assessed and compared with the MBA using four commercially important shellfish matrices, including cockles Cerastoderma edule, razor shells Solen marginatus, oysters Crassostrea gigas, and mussels Perna perna. Over 50 samples were collected and analysed as part of the regulatory monitoring framework including a suite of monthly samples from 2017 and all samples identified as toxic by MBA since 2011. Testing of reference material and evaluation of assay-critical parameters (e.g. slope of calibration curve, internal quality control QC and IC50) confirmed the robustness of the RBA methodology. With this RBA method, STX-like activity detected in shellfish samples ranged from 33 to 8500 μg STX equivalents per kg. RBA data were significantly correlated (P < 0.0001, Pearson r = 0.96) with the MBA-derived dataset. Importantly, the RBA method allowed for the detection and quantification of PSP toxins at levels not detectable by using the mouse bioassay. The limits of quantification of the RBA was calculated and found to be 10-fold lower than that of the MBA, respectively 35.24 ± 5.99 and 325 μg STX equivalents per kg of tissue. In addition, the RBA was easier to use and produced reliable results more rapidly than the MBA and without use of live animals. Considering the increasing risks associated with harmful algal blooms, globally and in Morocco, together with the increased development of aquaculture production and seafood consumption and the difficulties of live animal testing, these findings indicate that the RBA method is a reliable and effective alternative to the MBA method.

All currently available general anesthetic agents possess potentially lethal side effects requiring their administration by highly trained clinicians. Among these agents is etomidate, a highly potent imidazole-based intravenous sedative-hypnotic that deleteriously suppresses the synthesis of adrenocortical steroids in a manner that is both potent and persistent. We developed two distinct strategies to design etomidate analogs that retain etomidate\'s potent hypnotic activity, but produce less adrenocortical suppression than etomidate. One strategy seeks to reduce binding to 11β-hydroxylase, a critical enzyme in the steroid biosynthetic pathway, which is potently inhibited by etomidate. The other strategy seeks to reduce the duration of adrenocortical suppression after etomidate administration by modifying the drug\'s structure to render it susceptible to rapid metabolism by esterases. In this chapter, we describe the methods used to evaluate the hypnotic and adrenocortical inhibitory potencies of two lead compounds designed using the aforementioned strategies. Our purpose is to provide a case study for the development of novel analogs of existing drugs with reduced side effects.