Extended Whole-body Ga-68 DOTATATE PET-CT in evaluating Tumour-Induced Osteomalacia: Case report and review of literature.

Tumour-induced osteomalacia is a rare paraneoplastic syndrome that manifests as chronic hypophosphataemia, non-specific bone pain and muscle weakness. It is generally caused by phosphaturic mesenchymal tumour (PMT), which is uncommonly associated with synchronous tumours. However, diagnosis is often delayed for several years due to the rarity, indolent growing nature and non-specific symptoms of the disease, often resulting in an overlook by clinicians during assessments. The patient initially presented with hypophosphataemia and generalised skeletal pain with multiple atraumatic fractures. Blood tests revealed serum calcium levels at the upper limit and extremely low inorganic phosphate levels. Herein, we report a case where two synchronous PMTs from two different sites were detected by 'extended' whole-body Ga-68 DOTATATE PET-CT, leading to remission of the disease after complete surgical removal. Early detection and diagnosis of PMT neoplasm is crucial, as complete surgical resection of this tumour is the only definitive treatment currently known. Upon excision, this curable disease will result in complete resolution of symptoms and blood parameters, leading to remission of the disease which significantly improves the patient's quality of life. PMT often over-expresses somatostatin receptors (SSTR), predominantly subtype 2A, and Ga-68 DOTATATE PET-CT is a selective SSTR imaging that targets this characteristic over-expression in these tumours. The high diagnostic accuracy of Ga-68 DOTATATE PET-CT should be the primary imaging modality for full evaluation of this disease.

68Ga-PSMA PET/CT and 18F-FDG PET/CT in Renal Cell Carcinoma.

Recent case reports and series have demonstrated the usefulness of Ga/F-PSMA PET/CT in restaging recurrent renal cancer after nephrectomy. We presented a case of a patient with renal mass who had undergone both F-FDG and Ga-PSMA PET/CT for diagnosis and staging. Concordant tracer uptake in the primary tumor and metastatic lesions was demonstrated by both radiotracers. Final histopathological reports revealed clear cell renal cell carcinoma. Furthermore, unusual left metacarpal bone metastasis was also detected.

Optimisation of LRRK2 inhibitors and assessment of functional efficacy in cell-based models of neuroinflammation.

LRRK2IN1 is a highly potent inhibitor of leucine-rich repeat kinase 2 (LRRK2, IC50 = 7.9 nM), an established target for treatment of Parkinson's disease. Two LRRK2IN1 analogues 1 and 2 were synthesised which retained LRRK2 inhibitory activity (1: IC50 = 72 nM; 2: IC50 = 51 nM), were predicted to have improved bioavailability and were efficacious in cell-based models of neuroinflammation. Analogue 1 inhibited IL-6 secretion from LPS-stimulated primary human microglia with EC50 = 4.26 µM. In order to further optimize the molecular properties of LRRK2IN1, a library of truncated analogues was designed based on docking studies. Despite lacking LRRK2 inhibitory activity, these compounds show anti-neuroinflammatory efficacy at micromolar concentration. The compounds developed were valuable tools in establishing a cell-based assay for assessing anti-neuroinflammatory efficacy of LRRK2 inhibitors. Herein, we present data that IL-1ß stimulated U87 glioma cell line is a reliable model for neuroinflammation, as data obtained in this model were consistent with results obtained using primary human microglia and astrocytes.