Preliminary experience with small animal SPECT imaging on clinical gamma cameras

The traditional lack of techniques suitable for in vivo imaging has induced a great interest in molecular imaging for preclinical research. Nevertheless, its use spreads slowly due to the difficulties in justifying the high cost of the current dedicated preclinical scanners. An alternative for lowering the costs is to repurpose old clinical gamma cameras to be used for preclinical imaging. In this paper we assess the performance of a portable device, that is, working coupled to a single-head clinical gamma camera, and we present our preliminary experience in several small animal applications. Our findings, based on phantom experiments and animal studies, provided an image quality, in terms of contrast-noise trade-off, comparable to dedicated preclinical pinhole-based scanners. We feel that our portable device offers an opportunity for recycling the widespread availability of clinical gamma cameras in nuclear medicine departments to be used in small animal SPECT imaging and we hope that it can contribute to spreading the use of preclinical imaging within institutions on tight budgets

Relationship between serum prolactin levels and protein composition of breast secretions in nonlactating women

En esta interesante se describe la relación entre los niveles séricos de prolactina (PRL) basales y tras estimulación con hormona liberadora de tirotropina (TRH), y la composición proteica de la secreción del pezón en 54 mujeres premenopáusicas y no lactantes durante la fase lútea de su ciclo menstrual. Las mujeres incluidas en este estudio se clasificaron en cuatro grupos teniendo en cuenta la presencia o ausencia de patología mamaria y el patrón proteico de sus secreciones mamarias. Los fluidos mamarios tipo I contenían Zn-α2-glicoproteina, apolipoproteina D y la proteína 15 de la enfermedad macroquistica mamaria; mientras que los fluidos tipo II se caracterizaron por la presencia de algunas proteínas de la leche como la lactoferrina, lisozima y α-lactoalbumina. Los niveles basales de PRL, progesterona, LH, FSH, T3 y T4 estuvieron dentro de rangos normales y no se identificó ninguna diferencia entre los grupos de mujeres incluidas en el estudio. Sin embargo, después de una prueba de estimulación con TRH si se objetivaron diferencias entre los grupos. En ausencia de patología mamaria, el aumento de PRL fue significativamente superior en mujeres con secreciones tipo II frente a las que tenían secreción tipo I (64 ± 6.8 µg/L vs. 7 ± 3.9 µg/L, p<0.02). De manera similar, cuando se consideraron las concentraciones de PRL en pacientes con enfermedad mamaria benigna, aquellas con fluidos mamarios tipo II tuvieron un aumento de la PRL significativamente superior en comparación con las que tenían fluidos a las que les faltaban estas proteínas (77.1 ± 6.2 µg/L vs. 58.8 ± 5.1 µg/L; P<0.05). Estos resultados muestran que la presencia de proteínas de la leche en la secreción del pezón de mujeres no lactantes se asocia con un incremento de la PRL en el suero tras la estimulación con TRH. Con ello, se abre la posibilidad de utilizar este análisis como un procedimiento no invasivo para el estudio en el efecto putativo de la PRL en el desarrollo de enfermedades mamarias benignas y malignas.Comisión Interministerial de Ciencia y Tecnología, Plan Nacional de I

Analytical, experimental, and Monte Carlo system response matrix for pinhole SPECT reconstruction

Purpose: To assess the performance of two approaches to the system response matrix (SRM) calculation in pinhole single photon emission computed tomography (SPECT) reconstruction. Methods: Evaluation was performed using experimental data from a low magnification pinhole SPECT system that consisted of a rotating flat detector with a monolithic scintillator crystal. The SRM was computed following two approaches, which were based on Monte Carlo simulations (MC-SRM) and analytical techniques in combination with an experimental characterization (AE-SRM). The spatial response of the system, obtained by using the two approaches, was compared with experimental data. The effect of the MC-SRM and AE-SRM approaches on the reconstructed image was assessed in terms of image contrast, signal-to-noise ratio, image quality, and spatial resolution. To this end, acquisitions were carried out using a hot cylinder phantom (consisting of five fillable rods with diameters of 5, 4, 3, 2, and 1 mm and a uniform cylindrical chamber) and a custom-made Derenzo phantom, with center-to-center distances between adjacent rods of 1.5, 2.0, and 3.0 mm. Results: Good agreement was found for the spatial response of the system between measured data and results derived from MC-SRM and AE-SRM. Only minor differences for point sources at distances smaller than the radius of rotation and large incidence angles were found. Assessment of the effect on the reconstructed image showed a similar contrast for both approaches, with values higher than 0.9 for rod diameters greater than 1 mm and higher than 0.8 for rod diameter of 1 mm. The comparison in terms of image quality showed that all rods in the different sections of a custom-made Derenzo phantom could be distinguished. The spatial resolution (FWHM) was 0.7 mm at iteration 100 using both approaches. The SNR was lower for reconstructed images using MC-SRM than for those reconstructed using AE-SRM, indicating that AE-SRM deals better with the projection noise than MC-SRM. Conclusions: The authors' findings show that both approaches provide good solutions to the problem of calculating the SRM in pinhole SPECT reconstruction. The AE-SRM was faster to create and handle the projection noise better than MC-SRM. Nevertheless, the AE-SRM required a tedious experimental characterization of the intrinsic detector response. Creation of the MC-SRM required longer computation time and handled the projection noise worse than the AE-SRM.Nevertheless, the MC-SRM inherently incorporates extensive modeling of the system and therefore experimental characterization was not required

Clinicopathological characteristics of infiltrating lobular breast carcinoma in elderly women: Preliminary results

This study was conducted to investigate the clinicopathological parameters in elderly women (aged >70 years) with infiltrating lobular carcinoma (ILC) of the breast and compare the results with those obtained from younger patients (aged 55-70 years). The study sample included a total of 46 women with ILCs, 10 aged >70 and 36 aged 55-70 years. The parameters analysed were tumor size, histological grade (HG), axillary lymph node involvement, distant metastasis and immunohistochemical expression of estrogen, progesterone and androgen receptors, Ki67, p53 and B cell lymphoma 2. Compared to women aged 55-70 years, ILCs in women aged >70 years were commonly of larger size (P=0.068) and were more frequently HG3 (P=0.024). There were no statistically significant differences in the other parameters analysed. Furthermore, we were unable to determine differences in cancer recurrence and mortality in the two patient subgroups during our follow-up. In conclusion, our preliminary results, based on the limited number of cases included in this study, indicate that i) ILCs in women aged >70 years tended to be larger compared to those in women aged 55-70 years and were more frequently of grade 3; and ii) there were no significant differences in terms of recurrence and mortality between the two patient subgroups during our follow-up

Expression and prognostic significance of apolipoprotein D in breast cancer.

En esta publicación se evaluó la expresión y la significación pronostica de la apolipoproteína D (apo D) en 163 carcinomas mamarios. La apo D es una glicoproteína involucrada en el sistema de transporte de lípidos del plasma humano y presente en grandes cantidades en el líquido de los quistes de mujeres con enfermedad macroquistica mamaria. Además, se ha propuesto como marcador de la acción esteroidea en células de cáncer de mama. La técnica empleada para evaluar la expresión de Apo D en carcinomas de mama fue la tinción con inmunoperoxidasa. Del total, 103 tumores se tiñeron para la apo D con una amplia variabilidad en la intensidad y el porcentaje de positividad. Para la cuantificación de la tinción se utilizó el sistema HSCORE que considera tanto la intensidad de la tinción como el porcentaje de células teñidas. Los resultados de este estudio mostraron una asociación significativa entre la apo D y el estado menopáusico de pacientes y el grado de diferenciación de los tumores. Los valores de apo D fueron más bajos en tumores de mujeres premenopáusicas o en carcinomas pobremente diferenciados, sugiriendo el valor potencial de esta glicoproteína como factor pronóstico en cáncer de mama. Además, el análisis preliminar de supervivencia libre de enfermedad y supervivencia global en un subgrupo de 152 mujeres con un seguimiento medio de 42 meses confirmó que los valores bajos de apo D se asociaban significativamente con una supervivencia libre de enfermedad más corta y una supervivencia global más pobre. No encontramos ninguna correlación significativa entre la apo D y el tamaño del tumor, la afectación de los ganglios linfáticos o parámetros bioquímicos como los receptores de estrógenos, la catepsina D o la proteína pS2. Los resultados de este estudio fueron muy trascendentes ya que nos permitieron proponer que la apo D, en combinación con otros factores pronósticos bien establecidos, podría contribuir a identificar con mayor precisión a subgrupos de pacientes con cáncer de mama con bajo o alto riesgo de recaída y muerte. La importancia de esta publicación se ha visto refrendada en publicaciones recientes donde se ha corroborado que esta lipoproteína está relacionada con la gravedad del cáncer de mama

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

Cancer stem cells play an important role in carcinogenesis and resistance to treatment and may lead to metastasis. The isolation of circulating stem cells involves cell sorting based on the presence of cell surface markers. Many surface markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the present study, we determined the expression of different stem cell markers and their variation in expression at different stages of the treatment process. Samples of EDTA blood were collected from metastatic colorectal cancer patients, and circulating cancer stem cells were isolated for the analysis of the expression of stem cell markers using RT-PCR. These findings were correlated with the response to therapy. All statistical analyses were performed using the GraphPad Prism 5.03 software. Significant differences were found in the expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences were found in c-Kit expression. Correlation in the expression levels of most of the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a predictive value for colon cancer behavior. Evaluation of this stem cell gene expression panel may be useful for predicting the response during the process of treatment, and the relative easy access to samples facilitates this method. Moreover the correlation between CD133 and TWIST1 expression may be associated with tumor regrowth and metastatic relapse

Evaluation of Lu-177-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors

BACKGROUND: (177)Lu peptide receptor radionuclide therapy (PRRT) is a recently approved therapy in Spain that has been demonstrated to be a well-tolerated therapy for positive somatostatin receptor advanced gastroenteropancreatic neuroendocrine tumors. AIM: To determine the impact of PRRT on quality of life, radiologic and metabolic response, overall survival, prognostic factors and toxicity. METHODS: Thirty-six patients treated with (177)Lu-PRRT from 2016 to 2019 were included. The most frequent location of the primary tumor was the gastrointestinal tract (52.8%), pancreas (27.8%), and nongastropancreatic neuroendocrine tumor (11.1%). The liver was the most common site of metastasis (91.7%), followed by distant nodes (50.0%), bone (27.8%), peritoneum (25.0%) and lung (11.1%). Toxicity was evaluated after the administration of each dose. Treatment efficacy was evaluated by two parameters: stable disease and disease progression in response evaluation criteria in solid tumors 1.1 criterion and prognostic factors were tested. RESULTS: From 36 patients, 55.6% were men, with a median age of 61.1 +/- 11.8 years. Regarding previous treatments, 55.6% of patients underwent surgery of the primary tumor, 100% of patients were treated with long-acting somatostatin analogues, 66.7% of patients were treated with everolimus, 27.8% of patients were treated with tyrosine kinase inhibitor, and 27.8% of patients were treated with interferon. One patient received radioembolization, three patients received chemoembolization, six patients received chemotherapy. Hematological toxicity was registered in 14 patients (G1-G2: 55.5% and G3: 3.1%). Other events presented were intestinal suboclusion in 4 cases, cholestasis in 2 cases and carcinoid crisis in 1 case. The median follow-up time was 3 years. Currently, 24 patients completed treatment. Nineteen are alive with stable disease, two have disease progression, eight have died, and nine are still receiving treatment. The median overall survival was 12.5 mo (95% confidence interval range: 9.8-15.2), being inversely proportional to toxicity in previous treatments (P < 0.02), tumor grade (P < 0.01) and the presence of bone lesions (P = 0.009) and directly proportional with matching lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01), , primary tumor surgery (P = 0.03) and metastasis surgery (P = 0.045). In a multivariate Cox regression analysis, a high Ki67 index (P = 0.003), a mismatch in the lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01) and a preceding toxicity in previous treatments (P < 0.05) were risk factors to overall survival. CONCLUSION: Overall survival was inversely proportional to previous toxicity, tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery

A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID)

Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and is a considerable burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection-related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by increased bradykinin synthesis. Methods: ICAT-COVID is a multicenter, randomized, open-label, proof-of-concept phase II clinical trial assessing the clinical efficacy and safety of adding icatibant to the standard of care in patients hospitalized with COVID-19 without invasive mechanical ventilation. Patients hospitalized with a confirmed COVID-19 pneumonia diagnosis (RTPCR or antigen test <= 10 days prior to randomization, and radiographic evidence of pulmonary infiltrates), rated 4 or 5' on the WHO's clinical status scale, are eligible. Patients will be randomized on a 1:1 ratio to either standard of care-plus-icatibant (experimental group) or to standard of care alone (control group). The experimental group will receive 30 mg of icatibant subcutaneously 3 times a day for 3 days (for a total of 9 doses). The expected sample size is 120 patients (60 per group) from 2 sites in Spain. Primary outcomes are the efficacy and safety of Icatibant. The main efficacy outcome is the number of patients reaching grades 2 or 1 on the WHO scale within 10 days of starting treatment. Secondary outcomes include long-term efficacy: number of patients discharged who do not present COVID-19-related relapse or comorbidity up until 28 days after discharge, and mortality. Discussion: Icatibant, a bradykinin type 2 receptor antagonist with proven effectiveness and safety against hereditary angioedema attacks, may be beneficial for COVID-19 patients by inhibiting bradykinin's action on endothelial cells and by inhibiting the SARS-CoV-2 M protease. Our working hypothesis is that treatment with standard of care-plus-icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution