CITK Loss Inhibits Growth of Group 3 and Group 4 Medulloblastoma Cells and Sensitizes Them to DNA-Damaging Agents.

Medulloblastoma (MB) is the most common malignant brain tumor in children, and it is classified into four biological subgroups: WNT, Sonic Hedgehog (SHH), Group 3 and Group 4. The current treatment is surgery, followed by irradiation and chemotherapy. Unfortunately, these therapies are only partially effective. Citron kinase protein (CITK) has been proposed as a promising target for SHH MB, whose inactivation leads to DNA damage and apoptosis. D283 and D341 cell lines (Group 3/Group 4 MB) were silenced with established siRNA sequences against CITK, to assess the direct effects of its loss. Next, D283, D341, ONS-76 and DAOY cells were treated with ionizing radiation (IR) or cisplatin in combination with CITK knockdown. CITK depletion impaired proliferation and induced cytokinesis failure and apoptosis of G3/G4 MB cell lines. Furthermore, CITK knockdown produced an accumulation of DNA damage, with reduced RAD51 nuclear levels. Association of IR or cisplatin with CITK depletion strongly impaired the growth potential of all tested MB cells. These results indicate that CITK inactivation could prevent the expansion of G3/G4 MB and increase their sensitivity to DNA-damaging agents, by impairing homologous recombination. We suggest that CITK inhibition could be broadly associated with IR and adjuvant therapy in MB treatment.

Gamma camera calibrations for the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases.

PURPOSE: The aim was to calibrate gamma cameras in the framework of the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases. Equipments of several manufacturers and different models were used. METHODS: Eleven gamma cameras (3/8- and 5/8-inch crystal) were used, acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air, varying source-detector distance and source size. Transmission curves were measured, calculating the parameters used for attenuation/scatter correction with the pseudo-extrapolation number method, and assessing their variations with the source size. RESULTS: Values of the calibration factor (geometric mean of both detector sensitivities) ranged from 41.1 to 113.9cps/MBq. For the smallest source (diameter of 3.5cm), the calibration factor decrease ranged from -30% to -4%, highlighting the importance of partial volume effects according to the equipment involved. The sensitivity variation with the source-detector distance, with respect to the 15cm-value, reached 10% (in absolute value) in the range 5-30cm, but fixing the distance between the two heads, the calibration factor variation with the distance from the midline was within 3.6%. Appreciable variation of the transmission curves with the source size were observed, examining the results obtained with six gamma cameras. CONCLUSION: Assessments of sensitivity and transmission curve variations with source size should be regularly implemented in calibration procedures. The results of this study represent a useful compendium to check the obtained calibrations for dosimetric purposes.

A simple and accurate dosimetry protocol to estimate activity for hyperthyroidism treatment.

BACKGROUND: Aim of the study was to evaluate accuracy of different dosimetry protocols in estimating the required 131I activity to treat hyperthyroid patients. MATERIALS AND METHODS: Forty consecutive patients were analysed: twenty-eight Graves' disease; twelve autonomous thyroid nodule (ATN). Maximum-uptake, effective half-time and residence-time were estimated from Radioiodine Uptake Test. Residence-time was estimated using a bi-compartmental model. For 131I activity calculation, algorithms laid down in European Association of Nuclear Medicine (EANM) guidelines, ICRP 53 approach and a mono-exponential formula (ME), were compared with OLINDA/EXM results. RESULTS: Based on EANM guidelines, activities to be administered were 3% higher in Graves' disease (p = 0.001) and 3% higher in ATN (p = 0.046). Calculated activities using ICRP 53 approach were significantly lower compared to OLINDA/EXM: 33% in Graves' disease; 17% in ATN. Activities recommended by ME, were significantly higher: in Graves' disease 20%; 42% in ATN. CONCLUSIONS: Only EANM algorithm predict quite well, compared to OLINDA/EXM, the required activity to treat hyperthyroid patients.

Implementation of a program for quality assurance on leaf positioning accuracy using Gafchromic(®) RTQA2 films.

In radiotherapy treatments the correct dose delivery to the target volume and the consequent conservation of healthy tissues is affected by multileaf collimator (MLC) leaf positioning accuracy and reproducibility, mostly in intensity-modulated radiation therapy (IMRT): For this reason a quality assurance (QA) program is necessary to ensure the best treatment possible to each patient. The aim of this study is the implementation of a method using Gafchromic(®) RTQA 2 films to perform routine QA on the MLC, both for qualitative and quantitative analysis. A flatbed document scanner (Epson 10000XL) was used in conjunction with radiochromic detector; a scanning protocol was firstly defined to improve readout accuracy. RTQA2 films were irradiated with 6 MV X-rays at different dose levels to obtain calibration curve. To evaluate the leaf positioning accuracy in different conditions, a rhomboidal shape and a field consisting in three rectangular segments were selected. The images quantitative analysis was handled with a program developed in MATLAB to evaluate the differences between expected and measured leaves positions. The reproducibility and global uncertainty of the method were estimated to be equal to 0.5% and 0.6 mm, respectively. Moreover, a qualitative test was performed: A garden picket fence field, consisting in multiple segments 2 × 22 cm(2), was realized setting known leaves shifts to test the method sensitivity. The picket fence test shows that the method is able to detect displacements equal to 1 mm. The results suggest that Gafchromic(®) RTQA2 films represent a reliable tool to perform MLC routine QA.

A case of primary mediastinal Ewing's sarcoma / primitive neuroectodermal tumor presenting with initial compression of superior vena cava.

Ewing's sarcomas and peripheral primitive neuroectodermal tumors (ES/PNETs) are high grade malignant neoplasms. These malignancies are characterized by a chromosome 22 rearrangement, arise from bone or soft tissue, predominantly affect children and young adults, and are grouped in the Ewing family of tumors. Multimodality treatment programs are the treatment of choice. Primary localization of ES/PNET in the mediastinum is extremely rare. We describe a case of ES/PNET presenting as a mediastinal mass with tracheal compression and initial signs of superior vena cava in a 66-year-old woman.

99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular neoplasms: relationship to multidrug resistance protein expression.

UNLABELLED: Recently, thyroid (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintiscanning has been proposed in an attempt to preoperatively identify thyroid malignancies, but discrepant results have been reported for oncocytic lesions. The aim of this study was to investigate the usefulness of visual and semiquantitative analyses of (99m)Tc-MIBI scintigraphy for preoperatively characterizing thyroid nodules with indeterminate cytologic diagnoses, segregating in advance nononcocytic variants from those that are oncocytic. This study also aimed to analyze the relationship between (99m)Tc-MIBI images and P-glycoprotein (P-gp)/multidrug resistance-associated protein-1 (MRP1) immunohistochemical expression. METHODS: Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed as nononcocytic or oncocytic follicular neoplasm were prospectively studied. Visual and semiquantitative (99m)Tc-MIBI scanning was performed and the diagnoses of the lesions were histologically proven by subsequent thyroidectomy. Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical samples. RESULTS: Visual and semiquantitative (99m)Tc-MIBI scintiscans showed a low specificity in preoperatively discriminating malignant oncocytic lesions. In nononcocytic nodules, the semiquantitative method was more accurate than the visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in 78% of the lesions with a negative (99m)Tc-MIBI retention index, compared with 11% of lesions with a positive retention index, correlating most strongly with a negative (99m)Tc-MIBI RI in those cases with strong MRP1 apical expression. CONCLUSION: Semiquantitative (99m)Tc-MIBI scintigraphy is an adjunctive method to predict preoperatively the malignant behavior of nononcocytic follicular thyroid nodules indeterminate at fine-needle aspiration biopsy, with a potential impact on the definition of their clinical management. Moreover, the good correlation found between immunohistochemical apical expression of MRP1 and the scintigraphic findings supports the (99m)Tc-MIBI results and provides tissue information on the molecular mechanisms responsible for (99m)Tc-MIBI images in thyroid lesions.