Development and Preclinical Evaluation of [211At]PSAt-3-Ga: An Inhibitor for Targeted α-Therapy of Prostate Cancer.

The application of prostate-specific membrane antigen (PSMA)-targeted α-therapy is a promising alternative to ß--particle-based treatments. 211At is among the potential α-emitters that are favorable for this concept. Herein, 211At-based PSMA radiopharmaceuticals were designed, developed, and evaluated. Methods: To identify a 211At-labeled lead, a surrogate strategy was applied. Because astatine does not exist as a stable nuclide, it is commonly replaced with iodine to mimic the pharmacokinetic behavior of the corresponding 211At-labeled compounds. To facilitate the process of structural design, iodine-based candidates were radiolabeled with the PET radionuclide 68Ga to study their preliminary in vitro and in vivo properties before the desired 211At-labeled lead compound was formed. The most promising candidate from this evaluation was chosen to be 211At-labeled and tested in biodistribution studies. Results: All 68Ga-labeled surrogates displayed affinities in the nanomolar range and specific internalization in PSMA-positive LNCaP cells. PET imaging of these compounds identified [68Ga]PSGa-3 as the lead compound. Subsequently, [211At]PSAt-3-Ga was synthesized in a radiochemical yield of 35% and showed tumor uptake of 19 ± 8 percentage injected dose per gram of tissue (%ID/g) at 1 h after injection and 7.6 ± 2.9 %ID/g after 24 h. Uptake in off-target tissues such as the thyroid (2.0 ± 1.1 %ID/g), spleen (3.0 ± 0.6 %ID/g), or stomach (2.0 ± 0.4 %ID/g) was low, indicating low in vivo deastatination of [211At]PSAt-3-Ga. Conclusion: The reported findings support the use of iodine-based and 68Ga-labeled variants as a convenient strategy for developing astatinated compounds and confirm [211At]PSAt-3 as a promising radiopharmaceutical for targeted α-therapy.

PSMA-Targeting Radiopharmaceuticals for Prostate Cancer Therapy: Recent Developments and Future Perspectives.

Prostate cancer (PC) is the second most common cancer among men, with 1.3 million yearly cases worldwide. Among those cancer-afflicted men, 30% will develop metastases and some will progress into metastatic castration-resistant prostate cancer (mCRPC), which is associated with a poor prognosis and median survival time that ranges from nine to 13 months. Nevertheless, the discovery of prostate specific membrane antigen (PSMA), a marker overexpressed in the majority of prostatic cancerous tissue, revolutionised PC care. Ever since, PSMA-targeted radionuclide therapy has gained remarkable international visibility in translational oncology. Furthermore, on first clinical application, it has shown significant influence on therapeutic management and patient care in metastatic and hormone-refractory prostate cancer, a disease that previously had remained immedicable. In this article, we provide a general overview of the main milestones in the development of ligands for PSMA-targeted radionuclide therapy, ranging from the firstly developed monoclonal antibodies to the current state-of-the-art low molecular weight entities conjugated with various radionuclides, as well as potential future efforts related to PSMA-targeted radionuclide therapy.

Voluminous Laryngeal Schwannoma Treated with Endoscopic Laser Approach.

Laryngeal schwannomas are rare benign encapsulated neurogenic tumors that represent less than 1.5% of all benign laryngeal tumors. We report a case of voluminous laryngeal schwannoma that was incidentally found during endotracheal intubation for thyroidectomy in a 43-year-old woman with clinical findings, features of radiologic and histopathologic examinations. The tumor was removed by CO2 laser during microlaryngoscopy. In this case report, we present a challenging approach that can be used in diagnosis and treatment of laryngeal schwannomas. Complete removal of the tumor should be considered as the initial approach to minimize morbidity.

A simple method for the synthesis of N-difluoromethylated pyridines and 4-pyridones/quinolones by using BrCF2COOEt as the difluoromethylation reagent.

We describe a novel transition metal-free method for the synthesis of N-difluoromethylated pyridines and 4-pyridones/quinolones by using readily available ethyl bromodifluoroacetate as a fluorine source. The formation of N-difluoromethylated pyridines involves a two-step process in which N-alkylation by ethyl bromodifluoroacetate is followed by in situ hydrolysis of the ester and decarboxylation. Besides optimizing the N-difluoromethylation conditions and assessing the influence of steric and electronic effects on the outcome of the reaction, we have synthesized the N-difluoromethylated analogues of two fluorophores and demonstrated that their spectroscopic properties can be improved through replacement of N-CH3 group by N-CF2H.

Schwannoma of the extracranial portion of the accessory nerve presenting as spinal adenopathy.

Schwannomas are benign tumours arising from Schwann cells in the peripheral nerve. The schwannoma of the accessory nerve is a very rare entity. We report a case of Schwannoma of the extracranial accessory nerve. A 22-year-old man presented with a slow-growing mass, located on the right upper neck. The patient did not have any neurological deficit. CT scan showed a hypodense mass behind sternocleidomastoid muscle. The suspected diagnosis was an adenopathy of the accessory spinal chain. Surgery was done via transcervical approach. The histopathological analysis concluded with a diagnosis of schwannoma. No recurrence was noted at the follow-up examination 29 months after surgery.

Woakes' syndrome.

Woakes' syndrome is a rare entity defined as recurrent sinonasal polyposis with a consequent nasal pyramid deformity. Only a few cases are reported in the literature. The goal of this study is to present the features of Woakes' syndrome through a clinical case. A 42-year-old man presented with a history of ASA triad. He started self-medication for 5 years. He returned to the otorhinolaryngology department for the aggravation and persistence of symptoms. CT scans showed the deformity and thinning of the nasal bones. A functional endoscopic sinus surgery and correction of nasal pyramid deformity were performed. At 6 months' follow-up, good functional and aesthetic outcomes were observed. Woakes' syndrome was described more than 130 years ago. Treatment includes endoscopic sinonasal surgery and local treatment. Adequate management and good adherence to the therapeutic protocol could be factors to prevent this syndrome.