Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent.

Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (64Cu), a form of copper chloride (64CuCl2), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 (68Ga) as a radionuclide precursor for labelling radiopharmaceuticals used to investigate neuroendocrine tumors and prostate cancer. This emerging interest is also related to the nuclear properties of 64CuCl2 that make it an ideal theragnostic nuclide. Indeed, 64CuCl2 emits ß+ and ß- particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of 64CuCl2 for the radionuclide cancer therapy of copper-avid tumors. Recently, 64CuCl2 was successfully used to image prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Copper cancer uptake was related to the expression of human copper transport 1 (hCTR1) on the cancer cell surface. Biodistribution, toxicology and radiation safety studies showed its radiation and toxicology safety. Based on the findings from the preclinical research studies, 64CuCl2 PET/CT also holds potential for the diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and the detection of the intracranial metastasis of copper-avid tumors based on the low physiological background of radioactive copper uptake in the brain.

[Chronic nonbacterial osteomyelitis: description of three pediatric cases.] / Osteomielite cronica non-batterica: descrizione di tre casi pediatrici.

Chronic recurrent multifocal osteomyelitis (CRMO) or also called chronic non-bacterial osteomyelitis (CNO) is the most common autoinflammatory bone disease. It is characterized by the presence of symptomatic and non-symptomatic bone lesions, mono or multifocal. The main sites involved are the metaphyses of the long bones, the bones of the pelvis, the vertebrae, the clavicle, the mandible. Local symptoms include pain, swelling, and warmth in the absence or presence of fever. The inflammatory process can involve the skin (palmoplantar pustulosis or acne) and the intestine. Diagnosis is complex and uses imaging techniques (X-ray, total-body MRI, scintigraphy) as well as common laboratory tests aimed at identifying an inflammatory state. In doubtful cases, especially in the monofocal forms, it is mandatory to perform a biopsy examination to rule out malignancy. The differential diagnosis includes neoplastic diseases, chronic infections, metabolic diseases, traumatic outcomes. Treatment is not standardized and involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, sulfasalazine, methotrexate, TNF inhibitors and bisphosphonates based on the experience of the individual centers. We report the experience of our Center (Operative Unit of Pediatrics S. Anna Hospital in Ferrara) with the description of 3 clinical cases, diagnosed from 2016 to 2018, treated with bisphosphonates with good clinical response and remission in two of them, while one patient had an adverse reaction to pamidronate and was subsequently successfully treated with methotrexate.