Is SARS-CoV-2 vertical transmission still a current problem? A case report on a diagnosed SARS-CoV-2 infection with a positive sample of urines.

BACKGROUND AND AIM: Current data suggest little to no possibility of original COVID-19 transmission in pregnant women to the fetus during pregnancy or childbirth. Warning with Omicron new variants has decreased. CASE REPORT: A clinical case of a SARS-CoV-2 virus transplacental infection of a newborn, born at the end of 2022, from a mother who tested positive for Sars-covid-2 and positive IgM SARS-CoV-2 anti-virus. The newborn tested positive for SARS-CoV-2 12 hours after birth, and was clinically symptomatic after three days, an increase in IgM antibodies was not found, although the virus was identified in the urine samples through molecular tests. The insufficient time to determine the presence of antibodies and the immune system's state of immaturity can explain the lack of IgM in the newborn's blood at 14 days after birth. CONCLUSIONS: The Omicron SARS-CoV-2 keeps provoking infections among newborns, especially if the mother contracts it during the third trimester. The host response is most likely influenced by the newborn's peculiar state of immune immaturity. Just before birth, a positive nasal swab and the presence of a positive urine examination confirmed the diagnosis of intraplacental exposure. Research on the virus through molecular tests of urines can represent an additional technique when an aetiological framework of the infection is necessary and a distinction between congenital and post-natal forms.

A suspected hypervitaminosis A.

BACKGROUND AND AIM: Vitamin A toxicity is uncommon, but when it occurs can be serious and even fatal. A case vitamin A intoxication with high levels in liver tests, thrombocytopenia and appearance virosis. Laboratory testing is one of the most widely used diagnostic interventions supporting medical decisions of this phenomenon are necessary. CASE REPORT: Here, we report a case vitamin A intoxication with high levels in liver tests, thrombocytopenia and appearance virosis. The patient showed several clinical signs abdominal pain, including mild anemia and thrombocytopenia. CONCLUSIONS: We believe that Laboratory testing is one of the most widely used diagnostic interventions supporting medical decisions, and further investigations regarding the etiology and prevalence of this phenomenon are necessary. (www.actabiomedica.it).

Validation of the HPLC Analytical Method for the Determination of Chemical and Radiochemical Purity of Ga-68-DOTATATE.

Purpose of the Study: Ga-68-DOTA-peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumors imaging using positron emission tomography (PET). A new selective and sensitive high-pressure liquid chromatography (HPLC) method was developed for determining chemical and radiochemical purity of Ga-68-DOTATATE (PET) tracer. The identification of peaks was achieved on a symmetry C18 column 3 µm 120Å (3.0 mm × 150 mm spherical particles) using (A) water + 0.1% trifluoroacetic acid (TFA) and (B) acetonitrile + 0.1% TFA, as the mobile phases at a flow rate of 0.600 mL/min and monitored at 220 nm. The run time was 16 min. Materials and Methods: The method was validated to fulfill International Conference on Harmonization requirements and EDQM guidelines, and it included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision. Results: The calibration curve was linear over the concentration range from 0.5 to 3 µg/ml, with a correlation coefficient (r2) equal to 0.999, average coefficient of variation (CV%) 2%, and average bias% did not deviate more than 5% for all concentrations. The LOD and LOQ for DOTATATE were 0.5 and 0.1 µg/mL, respectively. The method was considered precise, obtaining coefficients of variation between 0.22% and 0.52% for intraday and 0.20% and 0.61% for interday precision. Accuracy of method was confirmed with average bias% that did not deviate more than 5% for all concentrations. Conclusion: All results were acceptable and this confirmed that the method is suitable for its intended use in routine quality control of Ga-68-DOTATATE to guarantee the high quality of the finished product before release.

Maintainance of diagnostic Laboratory during pandemic emergency (SARS-CoV-2) in a Small Hospital.

.

Performance and long-term consistency of five Galliform 68Ge/68Ga generators used for clinical Ga-68 preparations over a 4 year period.

BACKGROUND: Gallium-68 is a positron emitter for PET applications that can be produced without cyclotron by a germanium (Ge-68) chloride/gallium (Ga-68) chloride generator. Short half-life (67.71 min) of Ga-68, matching pharmacokinetic properties of small biomolecules, facilitates isotope utilization in compounding radiopharmaceuticals for PET imaging. The increasing cost of good manufacturing practice-compliant generators has strengthened the need for radionuclide efficient use by planning specific radiopharmaceutical sessions during the week, careful maintenance of the generator and achievement of high labeling yield and radiochemical purity (RCP) of the radiolabeled molecules. METHODS: The aim of this study was to evaluate the annual performance of five consecutive 68Ge/68Ga generators used for small-scale preparations of 68Ga-radiopharmaceuticals. To assess the long-term efficiency of isotope production we measured the weekly elution yield. To assess process efficiency we measured elution yield, labeling yield and RCP of four radiopharmaceutical preparations (68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68Ga-PENTIXAFOR and 68Ga-DOTATATE). RESULTS: The annual mean elution yield of the generators was 74.7%, higher than that indicated by the manufacturer, and it never went below 65%. The Ge-68 level in the final products was under the detection limits in all the produced batches (mean value 0.0000048%). The RCP of radiopharmaceuticals determined by high-performance liquid chromatography was 98 ± 0.22%. The mean yield of radiolabelling was 64.68, 68.71, 57 and 63.68% for 68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68GaPENTIXAFOR and 68Ga-DOTATATE. CONCLUSION: The ability to prepare in the hospital radiopharmacy high-purity and pharmaceutically acceptable 68Ga-radiolabeled probes on a routine basis facilitates patient access to precision imaging for clinical and research aims.

Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [68Ga]Ga-NODAGA-Exendin-4 Produced by a Fully Automated Method.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in ß-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R-avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic ß-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [68Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a 68Ge/68Ga Generator (GalliaPharma®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 µg/mL) and [68Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [68Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5-0.75 µg/mL for both the analytes (NODAGA-exendin-4 and 68Ga-NODAGA-exendin-4), with a correlation coefficient (R2) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [68Ga]Ga-NODAGA-exendin-4 was linear with a R2 of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 µg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [68Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [68Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [68Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

Feasibility of a Scale-down Production of [68Ga]Ga-NODAGA-Exendin-4 in a Hospital Based Radiopharmacy.

BACKGROUND: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in ß-cells, but it is highly expressed in human insulinomas and gastrinomas. Several GLP-1 receptor- avid radioligands have been developed to image insulin-secreting tumors or to provide a quantitative in vivo biomarker of pancreatic ß-cell mass. Exendin-4 is a high affinity ligand of the GLP1- R, which is a candidate for being labeled with a PET isotope and used for imaging purposes. OBJECTIVE: Here, we report the development and validation results of a semi-manual procedure to label [Lys40,Nle14(Ahx-NODAGA)NH2]exendin-4, with Ga-68. METHODS: A68Ge/68Ga Generator (GalliaPharma®, Eckert and Ziegler) was eluted with 0.1M HCl on an automated synthesis module (Scintomics GRP®). The peptide contained in the kit vial (Radioisotope Center POLATOM) in different amounts (10-20-30 µg) was reconstituted with 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethansulfonic acid (HEPES) solution and 68GaCl3 (400-900 MBq), followed by 10 min incubation at 95°C. The reaction solution was then purified through an Oasis HLB column. The radiopharmaceutical product was tested for quality controls (CQs) in accordance with the European Pharmacopoeia standards. RESULTS: The synthesis of [68Ga]Ga-NODAGA-Exendin-4 provided optimal results with 10 µg of peptide, getting the best radiochemical yield (23.53 ± 2.4%), molar activity (100 GBq/µmol) and radiochemical purity (91.69%). CONCLUSION: The study developed an imaging tool [68Ga]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.

18F-FDG and 68GA-Prostate-Specific Membrane Antigen PET/CT Perform Better Than CT Alone in Restaging Papillary Renal Cell Carcinoma Recurrence.

ABSTRACT: Renal cell carcinoma (RCC) shows variable FDG uptake; recently, PET/CT with prostate-specific membrane antigen (PSMA)-target radiotracers was demonstrated to be a promising tool in staging and restaging of RCC patients. We describe the case of a 77-year-old man with a lung metastasis of papillary RCC missed by CT scan who successfully underwent [18F]FDG PET/CT restaging. Targeted therapy with sunitinib was administered. A [68Ga]PSMA PET/CT performed during follow-up demonstrated, among the already known lesions, also a bone marrow metastasis, missed by previous CT scans. This case demonstrates that PET/CT molecular imaging with [18F]FDG and [68Ga]PSMA is superior to conventional imaging in RCC restaging and in assessing therapy response.

A Rapid and Specific HPLC Method to Determine Chemical and Radiochemical Purity of [68Ga]Ga-DOTA-Pentixafor (PET) Tracer: Development and Validation.

BACKGROUND: Due to its overexpression in a variety of tumor types, the chemokine receptor 4 (CXCR4) represents a highly relevant diagnostic and therapeutic target in nuclear oncology. Recently, [68Ga]Ga-DOTA-Pentixafor has emerged as an excellent imaging agent for positron emission tomography (PET) of CXCR4 expression in vivo. Preparation conditions may influence the quality and in vivo behaviour of this tracer and no standard procedure for the quality controls (QCs) is available. OBJECTIVE: The developed analytical test method was validated because a specific monograph in the Pharmacopoeia is not available for [68Ga]Ga-DOTA-Pentixafor. METHOD: A stepwise approach was used based on the quality by design (QbD) concept of the ICH Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of EANM, SNM, IAEA and WHO. RESULTS: The purity and quality of the radiopharmaceutical obtained according to the proposed method were found to be high enough to safely administrate it to patients. Excellent linearity was found between 0.5 and 4 µg/mL, with a correlation coefficient (r2) for calibration curves being equal to 0.999, the average coefficient of variation (CV%) < 2% and average bias% that did not deviate more than 5% for all concentrations. CONCLUSION: This study developed a new rapid and simple HPLC method of analysis for the routine QCs of [68Ga]Ga-DOTA-Pentixafor to guarantee the high quality of the finished product before release.

Unknown SARS-CoV-2 pneumonia detected by PET/CT in patients with cancer.

INTRODUCTION: In January 2020, the coronavirus disease 2019 (COVID-19) outbreak in Italy necessitated rigorous application of more restrictive safety procedures in the management and treatment of patients with cancer to ensure patient and staff protection. Identification of respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was a challenge during the pandemic owing to a large number of asymptomatic or mildly symptomatic patients. METHODS: We report 5 patients with unknown SARS-CoV-2 infection undergoing positron emission tomography (PET)/computed tomography (CT) with radiopharmaceuticals targeting different tumor processes: 18F-FDG, 18F-choline (FCH), and 68Ga-PSMA. RESULTS: In all patients, PET/CT showed increased tracer uptake in the lungs corresponding to CT findings of SARS-CoV-2 pneumonia. Quantitative assessment of tracer uptake showed more elevated values for the glucose analogue 18F-FDG (mean SUVmax 5.4) than for the other tracers (mean SUVmax 3.5). CONCLUSIONS: Our findings suggest that PET/CT is a sensitive modality to hypothesize SARS-CoV-2 pneumonia in patients with cancer, even when asymptomatic. More data are needed to verify the correlation among immune response to SARS-CoV-2 infection, clinical evolution, and PET results. Under the strict safety measures implemented at the PET center, the number of potentially SARS-CoV-2-positive patients undergoing PET/CT was very low (1.6%), and no staff member has been diagnosed with infection as of April 30, 2020.

Synthesis, validation and quality controls of [68Ga]-DOTA-Pentixafor for PET imaging of chemokine receptor CXCR4 expression.

BACKGROUND: Chemokine receptor-4 (CXCR4) is involved in tumor growth and progression in several types of human cancer. Recently, [68Ga]-DOTA-Pentixafor has been assessed as an excellent imaging probe targeting CXCR4-expression using positron emission tomography (PET). Here we report on the entire production cycle of [68Ga]-DOTA-Pentixafor, including quality control development and process validation. METHODS: Synthesis of [68Ga]-DOTA-Pentixafor was validated via three independent and consecutive production runs using an automated synthesis system. All validation runs must pass the pre-set quality control (QC) limits. Validation was performed for established QC tests to ensure that methods were reproducible and reliable in routine use. Germanium-68 breakthrough was determined for each sample. Production yield was calculated for each synthesis to assess the performance and efficiency of the radiolabeling process. The quality of the final product was determined by ITLC and HPLC methods after each synthesis. RESULTS: The average ITLC-measured radiochemical purity was above 98.5% and HPLC-measured radiochemical purity was 99.86%, 99,83% and 100% in the three validation runs. Germanium breakthrough was 4.8*10-5%, 4.9*10-5% and 4.7*10-5% of total activity, far below the recommended level of 0.001%. Residual ethanol resulted 5.22%, 5.58% and 5.32%V/V; spot of HEPES impurity was not more intense than spot of reference solution (200µg/V). Endotoxin level resulted <17.5EU/ml. pH of the final product was 7 in all samples. CONCLUSION: [68Ga]-DOTA-Pentixafor fit requirements of the pre-set quality parameters of purity, efficacy and safety in the batches considered for this study  and fulfilled all the acceptance criteria for injectable radiopharmaceutical products. The results demonstrated a batch-to-batch reproducibility providing high radiochemical purity.

SPECT/CT with 99mTc labelled heat-denatured erythrocyte to detect thoracic and abdominal splenosis.

Scintigraphy with 99mTc labelled heat-denatured erythrocyte (DRBC) allows non invasive diagnosis of heterotopic splenic tissue implantation (splenosis) following splenic trauma or surgery. Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) improves diagnostic accuracy of planar imaging through a more precise localization of functional findings. We report about two cases of splenosis occurring many years after splenectomy. 99MTc-DCRBC scintigraphy was used for differential diagnosis of metasttic disease in one case and to assess an incidental finding at bone scan in the second one. SPECT/CT increased specificity of planar imaging, expecially revealing combined (thoracic and abdominal) splenosis.

Validation of Quality Control Parameters of Cassette-Based Gallium-68-DOTA-Tyr3-Octreotate Synthesis.

PURPOSE OF THE STUDY: Gallium (Ga)-68-DOTA peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumor imaging using positron emission tomography. However, at the moment, a specific monograph in the European Pharmacopoeia (Ph. Eur.) does exist only for Ga-68-edotreotide (DOTATOC) injection. Here, we report on the validation process of Ga-68-DOTA-Tyr3-octreotate (DOTATATE) cassette-based production and quality control (QC). MATERIALS AND METHODS: Preparation of Ga-68-DOTATATE was performed according to the current European Union-good manufacturing practices, the current good radiopharmacy practice, the Ph. Eur., and the guidelines on validation of analytical methods for radiopharmaceuticals. Process was validated via three consecutive production runs to ensure that the methods are reproducible and reliable in routine use. The QC tests for Ga-68-DOTATATE were radiochemical purity (RCP - high-pressure liquid chromatography [HPLC]), radiochemical impurities 68Ga3+ (HPLC and instant thin layer chromatography [ITLC]), chemical purity (HPLC and gas chromatography [GC]), pH (pH-strips), radionuclidic purity (principal γ-photon), germanium-breakthrough (68Ge-content), Ga-68 half-life (γ-ray spectrometry), and sterility/endotoxin assay. RESULTS: Radiolabeling procedure of Ga-68-DOTATATE fits all the applicable Ph. Eur. specifications. RCP measured via ITLC was >99% in the three validation batches. HPLC-measured RCP resulted 99.45%, 99.78%, and 99.75%. Germanium-breakthrough was far below the recommended level established in the Ph. Eur. Ga-68-DOTATOC injection (#2482). Residual ethanol tested with GC was less than 10%. All the batches were tested for endotoxin content, which always resulted lower than 17.5 EU/ml. All preparations passed the sterility tests. pH of the final product was 7 in all samples. CONCLUSION: Ga-68-DOTATATE fulfilled all the pre-set QCs and release criteria in the batches considered for this validation study. The results demonstrated a batch-to-batch reproducibility, ensuring that synthesis process leads to the expected final product in terms of yield, quality, reliability, safety, and efficacy.

Validation of in vitro labeling method for human use of heat-damage red blood cells to detect splenic tissue and hemocateretic function.

BACKGROUND AND AIM: Selective imaging of the splenic tissue is obtained with heat-damaged, or heat-denatured, red blood cells (RBCs) of the patient labeled with 99mTc in a variety of clinical scenarios. Aim of the study was to validate the process used for labelling heat-damaged red blood cells "totally in vitro", after blood sample collection, before re-inject labeled RBCs to the patient. Moreover, we assessed efficacy of the staff training programme in order to guarantee repeatibility and method standardization in the clinical routine. METHODS: The validation process of the labeling procedure was performed in three different patients during three consecutive days. After collection of a blood sample using a heparinized syringe, we isolated erythrocytes from other blood components by centrifugation and washing steps. Then, we added the stannous pyrophosphate (PYP) to the erythrocytes pellet, after  pH control. The 'pretinning' of RBCs was necessary to reduce Tc-99m once pertechnetate was entered them. After the labeling reaction with 130 MBq of 99mTc-pertechnetate, the erythrocytes were denatured in a water bath at a temperature of 49°-50°C, for 10 min. Radioactivity of blood aliquotes was measured with a dose calibrator and labelling efficiency (LE%) was determined. The labelling purity was measured using a gamma counter  and calculated using the formula: counts of pellet/counts of pellet+(counts of surnatant)*100.Training program was evaluated using a Learning Questionnaire (LQ). with a grading score from 6 ("") to 1 ("nothing") for each operator (n=3). RESULTS: We didn't observed the presence of macroaggregates during the entire process, until the final sample. The labelling efficiency resulted at very high values in the three consecutive measured aliquotes (mean value 73.67%) as well as the labelling purity (>95.22%). In our instituion, we use splenic imaging with labelled heat-damaged RBCs to detect ectopic spleen, splenosis, extramedullary hematopoiesis. We performed 3 procedures with  heat-damaged labeled RBCs with a  mean labelling efficiency 73.67%.Training and learning programmes were scored by key objective areas with a mean value of 5. CONCLUSIONS: Our in vitro labeling process of heat-damaged RBCs is simple and safe, providing a useful technique  easy to implement in clinical routine for splenic imaging Learning outcome of the training programme was scored as effective by all the operators with evidence of high-efficiency-reproducible procedure mantained over time.

Novel approach for quality assessment and improving diagnostic accuracy in cell-based infection imaging using 99mTc-HMPAO labeled leukocytes.

BACKGROUND AND AIM: Labeled leukocytes with 99mTc-HMPAO are routinely used for infection imaging. Although cell labeling with 99mTc-HMPAO represents an imaging probe to detect infection sites, the diagnostic efficiency of the probe is largely influenced by cell manipulation, multidisciplinary interventions (i.e., biologist, technicians) and available technology (i.e., SPECT, SPECT/CT). The aim of the study was to assess in vitro and in vivo accuracy of a comprehensive approach for quality assessment (QA) of all steps of the procedure. METHODS: Radiochemical purity (RCP), pH, labeling efficiency (LE) were measured in 320 procedures. White Cell Viability Factor (WVF) was determined in consecutive blood samples. Images (490 studies) were scored using a 5-point scale. Training program was evaluated using a Learning Questionnaire and a score system. RESULTS: Pre/post-labelling WVF was 0.99% (max value 1%) in all blood samples. LE (mean value 72%) and RCP (>80% until 55 minutes) yielded considerably high values. The vast majority of images were scored as diagnostic by three independent observer (90% with score ≥4). CONCLUSIONS: This method appears highly reproducible and easy to use in clinical routine for leukocyte labeling, especially when standardized training and total QA system are implemented.

Development and Validation of a High-Pressure Liquid Chromatography Method for the Determination of Chemical Purity and Radiochemical Purity of a [68Ga]-Labeled Glu-Urea-Lys(Ahx)-HBED-CC (Positron Emission Tomography) Tracer.

Background: Prostate-specific membrane antigen (PSMA) has gained high attention as a useful biomarker in the imaging evaluation of prostate cancer with positron emission tomography (PET) during recent years. [68Ga]-labeled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]-PSMA-HBED-CC) is a novel PSMA inhibitor radiotracer which has demonstrated its suitability in detecting prostate cancer. Preparation conditions may influence the quality and in vivo behavior of this tracer, and no standard procedure for the quality control (QC) is available. The aim of this study was to develop a new rapid and simple high-pressure liquid chromatography method of analysis for the routine QCs of [68Ga]-PSMA-HBED-CC to guarantee the high quality of the radiopharmaceutical product before release. Methods: A stepwise approach was used based on the quality by design concept of the International Conference of Harmonisation Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of European Association of Nuclear Medicine, Society of Nuclear Medicine, International Atomic Energy Agency, World Health Organization, and Italian Association of Nuclear Medicine and Molecular Imaging. The developed analytical test method was validated because a specific monograph in the pharmacopoeia is not available for [68Ga]-PSMA-HBED-CC. Results: The purity and quality of the radiopharmaceutical obtained according to the proposed method resulted high enough to safely administrate it to patients. An excellent linearity was found between 0.8 and 5 µg/mL, with a detection limit of 0.2 µg/mL. Assay imprecision (% CV) was <2%. Conclusions: The developed method to assess the radiochemical and chemical purity of [68Ga]-PSMA-HBED-CC is rapid, accurate, and reproducible, allowing routinely the use of this PET tracer as a diagnostic tool for imaging prostate cancer and also assuring patient safety.

Granulomatous Mastitis during Chronic Antidepressant Therapy: Is It Possible a Conservative Therapeutic Approach?

Granulomatous mastitis is a rare benign inflammatory disease of the breast with multiple etiologies such as tuberculosis, sarcoidosis, foreign body reaction, and mycotic and parasitic infections. In contrast, idiopathic granulomatous mastitis (IGM) is characterized by the presence of chronic granulomatous lobulitis in the absence of an obvious etiology. Clinically and radiologically it may mimic breast carcinoma and so awareness of surgeons, pathologists, and radiologists is essential to avoid unnecessary mastectomies. Cases of IGM are reported during antidepressant therapy in patients also showing high levels of prolactinemia. In these cases, we believe that surgical excision must be avoided being replaced with a conservative management of the pathological condition based on a corticosteroid treatment.

A complex case of fatal calciphylaxis in a female patient with hyperparathyroidism secondary to end stage renal disease of graft and coexistence of haemolytic uremic syndrome.

BACKGROUND: Calciphylaxis is a potentially fatal complication of persistent secondary hyperparathyroidism; its cause is still not clear. Unfortunately there is no close relation in severity of clinical picture, serological and pathological alteration. For this reason the prognosis is difficult to establish. Administration of sodium thiosulphate may reduce the precipitation of calcium crystals and improve the general clinical conditions before surgical parathyroidectomy, which seems the only therapeutic approach able to reduce the mortality risk in these patients. METHODS AND RESULTS: A 60 year old female patient suffering from End Renal Stage Disease, on haemodialysis from 2001 due to the onset of haemolytic uremic syndrome, underwent a kidney transplant in April 2008. After transplantation there was a recurrence of the haemolytic uremic syndrome, with temporary worsening of the graft. Six months later there was a definite loss of graft and return to dialysis treatment. On April 2010 a severe systemic calciphylaxis related to secondary hyperparathyroidism was diagnosed. The patient underwent parathyroidectomy but, because of the unimproved clinical picture, treatment with sodium thiosulphate was initiated. There was only improvement in cutaneous lesions. The worsening general clinical condition of the patient caused death due to general septic complications. CONCLUSIONS: The coexistence of haemolytic uremic syndrome and secondary hyperpathyroidism makes the prognosis poor and, in this case, therapy, which counteracts calcium crystals precipitation, has no effect. Preventive parathyroidectomy can be considered as the only possible treatment.