Ongoing studies of physiological and pathological processes have led to a corresponding need for new radiopharmaceuticals, especially when studies are limited by the absence of a particular radiolabeled target. Thus, the development of new radioactive tracers is highly relevant and can represent a significant contribution to efforts to elucidate important phenomena in biology. Currently, theranostics represents a new frontier in the fields of medicine and nuclear medicine, with the same compound being used for both diagnosis and treatment. In the human body, copper (Cu) is the third most abundant metal and it plays a crucial role in many biological functions. Correspondingly, in various acquired and inherited pathological conditions, such as cancer and Alzheimer’s disease, alterations in Cu levels have been found. Moreover, a wide spectrum of neurodegenerative disorders are associated with higher or lower levels of Cu, as well as inappropriately bound or distributed levels of Cu in the brain. In human cells, the membrane protein, hCtr1, binds Cu in its Cu(I) oxidation state in an energy-dependent manner. Copper-64 (⁶⁴Cu) is a cyclotron-produced radionuclide that has exhibited physical properties that are complementary for diagnosis and/or therapeutic purposes. To date, very few reports have described the clinical development of ⁶⁴Cu as a radiotracer for cancer imaging. In this review, we highlight recent insights in our understanding and use of ⁶⁴CuCl₂ as a theranostic agent for various types of tumors. To the best of our knowledge, no adverse effects or clinically observable pharmacological effects have been described for ⁶⁴CuCl₂ in the literature. Thus, ⁶⁴Cu represents a revolutionary radiopharmaceutical for positron emission tomography imaging and opens a new era in the theranostic field.

Background: The detection of sub-clinical breast lesions has increased with screening mammography. Biopsy techniques can offer precision and agility in its execution, as well as patient comfort. This trial compares radioguided occult lesion localization (ROLL) and wire-guided localization (WL) of breast lesions. We investigate if a procedure at the ambulatorial level (ROLL) could lead to a better aesthetic result and less postoperative pain. In addition, we intend to demonstrate the efficacy of radioguided localization and removal of occult breast lesions using radiopharmaceuticals injected directly into the lesions and correlate radiological and histopathological findings. Methods: One hundred and twenty patients were randomized into two groups (59 WL and 61 ROLL). The patients were requested to score the cosmetic appearance of their breast after surgery, and a numerical rating scale was used to measure pain on the first postoperative day. Clearance margins were considered at ≥ 10 mm for invasive cancer, ≥ 5 mm for ductal carcinoma in situ, and ≥ 1 mm for benign disease. Patients were subsequently treated according to the definitive histological result. When appropriate, different statistical tests were used in order to test the significance between the two groups, considering a P value < 0.05 as statistically significant. Results: WL and ROLL located all the occult breast lesions successfully. In the ROLL group, the specimen volume was smaller and there were more cases with clear margins (P < 0.05). There were significant differences in mean time of hospital stay between WL and ROLL (21.42 vs. 2.56 hours), but not in operative time (39.4 vs. 29.9 minutes). There were significant differences in the subjective ease of the procedures as rated by the patients (cosmetic outcomes and postoperative pain). Conclusion: ROLL is an effective method for the excision of non-palpable breast lesions. It enables more careful planning of the cutaneous incision, leading to better aesthetic results, less postoperative symptoms, and smaller volumes of excised tissue.

Even though mesenchymal stromal cells (MSCs) mitigate lung and distal organ damage in experimental polymicrobial sepsis, mortality remains high. We investigated whether preconditioning with eicosapentaenoic acid (EPA) would potentiate MSC actions in experimental sepsis by further decreasing lung and distal organ injury, thereby improving survival. In C57BL/6 mice, sepsis was induced by cecal hligation and puncture (CLP); sham-operated animals were used as control. Twenty-four hours after surgery, CLP mice were further randomized to receive saline, adipose tissue-derived (AD)-MSCs (105, nonpreconditioned), or AD-MSCs preconditioned with EPA for 6 h (105, EPA-preconditioned MSCs) intravenously. After 24 h, survival rate, sepsis severity score, lung mechanics and histology, protein level of selected biomarkers in lung tissue, cellularity in blood, distal organ damage, and MSC distribution (by technetium-99m tagging) were analyzed. Additionally, the effects of EPA on the secretion of resolvin-D1 (RvD1), prostaglandin E2 (PGE2), interleukin (IL)-10, and transforming growth factor (TGF)-β1 by MSCs were evaluated in vitro. Nonpreconditioned and EPA-preconditioned AD-MSCs exhibited similar viability and differentiation capacity, accumulated mainly in the lungs and kidneys following systemic administration. Compared to nonpreconditioned AD-MSCs, EPA-preconditioned AD-MSCs further reduced static lung elastance, alveolar collapse, interstitial edema, alveolar septal inflammation, collagen fiber content, neutrophil cell count as well as protein levels of interleukin-1β and keratinocyte chemoattractant in lung tissue, and morphological abnormalities in the heart (cardiac myocyte architecture), liver (hepatocyte disarrangement and Kupffer cell hyperplasia), kidney (acute tubular necrosis), spleen (increased number of megakaryocytes and lymphocytes), and small bowel (villi architecture disorganization). EPA preconditioning of MSCs resulted in increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β). Compared to nonpreconditioned cells, EPA-preconditioned AD-MSCs yielded further reductions in the lung and distal organ injury, resulting in greater improvement in sepsis severity score and higher survival rate in CLP-induced experimental sepsis. This may be a promising therapeutic approach to improve outcome in septic patients.

This is a pilot clinical study primarily designed to assess the feasibility and safety of X-ray-guided percutaneous intraspinal injection of allogeneic canine adipose tissue-derived mesenchymal stem cells in dogs with chronic spinal cord injury. Six dogs with chronic paraplegia (≥six months) were intraparenchymally injected with allogeneic cells in the site of lesion. Cells were obtained from subcutaneous adipose tissue of a healthy dog, cultured to passage 3, labeled with ^99mTechnetium, and transplanted into the lesion by percutaneous X-ray-guided injection. Digital X-ray efficiently guided cell injection as ^99mTechnetium-labeled cells remained in the injection site for at least 24 hours after transplantation. No adverse effects or complications (infection, neuropathic pain, or worsening of neurological function) were observed during the 16-week follow-up period after transplantation. Three animals improved locomotion as assessed by the Olby scale. One animal walked without support, but no changes in deep pain perception were observed. We conclude that X-ray-guided percutaneous intraspinal transplantation of allogeneic cells in dogs with chronic spinal cord injury is feasible and safe. The efficacy of the treatment will be assessed in a new study involving a larger number of animals.

Silicosis is an occupational disease for which no effective treatment is currently known. Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has shown to be safe in lung diseases. However, so far, no studies have analyzed whether bronchoscopic instillation of autologous BMDMCs is a safe route of administration in patients with silicosis. We conducted a prospective, non-randomized, single-center longitudinal study in five patients. Inclusion criteria were age 18–50 years, chronic and accelerated silicosis, forced expiratory volume in 1 s 40 %, forced vital capacity ≥60 % and arterial oxygen saturation >90 %. The exclusion criteria were smoking, active tuberculosis, neoplasms, autoimmune disorders, heart, liver or renal diseases, or inability to undergo bronchoscopy. BMDMCs were administered through bronchoscopy (2 × 107 cells) into both lungs. Physical examination, laboratory evaluations, quality of life questionnaires, computed tomography of the chest, lung function tests, and perfusion scans were performed before the start of treatment and up to 360 days after BMDMC therapy. Additionally, whole-body and planar scans were evaluated 2 and 24 h after instillation. No adverse events were observed during and after BMDMC administration. Lung function, quality of life and radiologic features remained stable throughout follow-up. Furthermore, an early increase of perfusion in the base of both lungs was observed and sustained after BMDMC administration. Administration of BMDMCs through bronchoscopy appears to be feasible and safe in accelerated and chronic silicosis. This pilot study provides a basis for prospective randomized trials to assess the efficacy of this treatment approach. NCT01239862 Date of Registration: November 10, 2010

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