International Comparison Exercise for Biological Dosimetry after Exposures with Neutrons Performed at Two Irradiation Facilities as Part of the BALANCE Project.

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated, and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0-4 Gy at two different facilities in Germany (Physikalisch-Technische Bundesanstalt [PTB]) and the USA (the Columbia IND Neutron Facility [CINF]). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semiautomatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semiautomatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed nonlinear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts.

Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents.

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO)5 and fac-[NEt4]2[ReBr3(CO)3] were used for the preparation of the Re complexes fac-[Re(NNO)(CO)3] (5a) and fac-[Re(SNO)(CO)3] (7a) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac-[99mTc(CO)3]+ core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac-[99mTc][Tc(OH2)3(CO)3]+ precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC50 = 8.85 ± 2.62 µM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC50 value of 26.11 nM. Biodistribution studies of the 99mTc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system.

Synthesis and preclinical evaluation of rhenium and technetium-99m "4 + 1" mixed-ligand complexes bearing quinazoline derivatives as potential EGFR imaging agents.

Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m (99mTc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new "4 + 1" mixed-ligand ReIII- and 99mTcIII-complexes of the general formula [99mTc][Tc(NS3)(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS3) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand. The quinazoline isocyanide derivatives 4a-d were prepared in two steps and reacted with the [Re(NS3)PMe2Ph] precursor leading to the final complexes 5a-d in high yield. All compounds were characterized by elemental analysis, IR, and NMR spectroscopies. In vitro studies, for their potency to inhibit the cell growth, using intact A431 cells indicate that the quinazoline derivatives 4a-d and the Re complexes 5a-d significantly inhibit the A431 cell growth. In addition, the EGFR autophosphorylation study of complex 5b shows an IC50 value in the nanomolar range. The corresponding "4 + 1" 99mTc-complexes 6a-d were prepared by employing the [99mTc]TcEDTA intermediate and the appropriate monodentate 4a-d in a two-step synthetic procedure with a radiochemical yield (RCY) from 63 to 77 % and a radiochemical purity (RCP) > 99 % after HPLC purification. Their structures have been established by HPLC comparative studies using the well-characterized Re-complexes 5a-d as reference. All 99mTc-complexes remain stable for at least 6 h, and their logD7.4 values confirmed their anticipated lipophilic character. Biodistribution studies in healthy Swiss albino mice of 99mTc-complexes showed hepatobiliary excretion and initial fast blood clearance. Complex 6b was also tested in Albino SCID mice bearing A431 tumors and showed rapid tumor uptake at 5 min (2.80 % ID/g) with a moderate tumor/muscle ratio (2.06) at 4 h p.i. The results encourage further investigation for this type of 99mTc-complexes as single-photon emission computed tomography (SPECT) radio agents for imaging tumors overexpressing EGFR.

Development and implementation of a quality control protocol for B-mode ultrasound equipment.

PURPOSE: Quality assurance (QA) of ultrasound (US) equipment is currently required in only a few countries around the world. In Greece, no national or other norms exist for regulating the use of US equipment. However, to obtain accreditation for the radiology department of a Greek hospital, the establishment and implementation of a quality control (QC) protocol and a QA programme for US equipment was required. MATERIALS AND METHODS: A literature review regarding US QC/QA procedures was performed. The information collected was used as a guide to create a QC/QA protocol and to obtain an appropriate US QC phantom. Drafting and testing of the initial protocol lasted 6 months. Its final version was implemented for 18 months in two US systems and five US transducers. RESULTS: The QC tests included in the protocol evaluate mechanical and electrical safety, image display, uniformity, penetration depth, distance accuracy, greyscale display, anechoic object imaging, geometric distortion, and axial/lateral resolution. The only QC test that failed was the test for uniformity since intense non-uniformities were observed that led to the replacement of two linear transducers. CONCLUSION: US imaging is considered safe and, where appropriate, is preferred over imaging modalities that use ionizing radiation. However, the lack of QC/QA implies that US image quality is not routinely monitored. Therefore, the possibility of malfunctions that may go undetected and lead to wrong diagnosis cannot be excluded. A QC/QΑ programme can contribute to the elimination of such errors and ensure that performance is maintained over time.

RENEB/EURADOS field exercise 2019: robust dose estimation under outdoor conditions based on the dicentric chromosome assay.

PURPOSE: Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life exposure scenarios. MATERIALS AND METHODS: For the dicentric chromosome assay (DCA), blood tubes were located at anthropomorphic phantoms positioned in different geometries and were irradiated with a 1.36 TBq 192Ir-source. For each exposure condition, dose estimates were provided by at least one laboratory and for four conditions by 17 participating RENEB laboratories. Three radio-photoluminescence glass dosimeters were placed at each tube to assess reference doses. RESULTS: The DCA results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for reference doses as well as for DCA doses estimates. CONCLUSIONS: The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation.

Quality assurance protocol for superficial and deep hyperthermia systems established by the Hellenic Association of Medical Physicists (HAMP) in cooperation with the Hellenic Society of Oncologic Hyperthemia (HSOH): A study based on European Society for Hyperthermic Oncology (ESHO) quality assurance guidelines.

PURPOSE: During the last years hyperthermia is a developing therapeutic modality in Greece. Quality assurance (QA) procedures are essential for ensuring the correct operation of the hyperthermia system and therefore the selective heating of the tumor with minimum toxicity to the surrounding healthy tissues. The European Society for Hyperthermic Oncology (ESHO) has proposed QA guidelines for superficial as well as deep hyperthermia systems. The purpose of this study was to describe the adapted QA protocol for superficial and deep hyperthermia systems established in Greece. METHODS: A working group was created by the Hellenic Association of Medical Physicists (HAMP) for the proposal of QA guidelines for superficial and deep hyperthermia systems. A review of the protocol proposed by ESHO, together with the existing protocols in other European and International centers, as well as protocols suggested by European or International organizations, was performed. Then, a protocol was suggested, describing procedures for QA according to the current technology and the existing equipment used in Greece. RESULTS: A protocol describing the procedures for QA of superficial and deep hyperthermia systems was proposed. These procedures aim to evaluate the correct operation of the device, the thermometric system, the generator, the incorporated power meter and the applicators. It will also ensure the electrical safety of the devices. CONCLUSIONS: The proposed protocol, applied by medical physicists in Greece, will ensure an efficient treatment with safety and minimum adverse effects. This protocol has been approved by the Hellenic Society of Oncologic Hyperthermia and the Hellenic Association of Medical Physicists.

Participation of women medical Physicists in European scientific events: The European experience.

PURPOSE: Though the number of women scientists is increasing over the years, studies show that they are still under-represented in leadership roles. The purpose of this work is to establish the percentage of women Medical Physicists (wMPs) that have participated in European scientific events and evaluate it as an indication of the current position of women in the field of Medical Physics in Europe and to propose possible ways to encourage their participation. MATERIALS AND METHODS: Data regarding the participants in European scientific events of Medical Physics were collected. The participants were divided into categories according to the program of the events and their gender was identified. The percentage of wMPs in each category was evaluated. RESULTS: The participation of wMPs attending courses is greater than 50%. The categories with the greatest participation are "Organizing Committees", "Chairpersons-Moderators" and "Oral Presentations". The categories with the lower participation of wMPs are "Scientific Committee", "Symposiums" and "Invited Speakers". None of wMPs were represented as "Course Directors". CONCLUSIONS: The attendance of wMPs in courses is slightly greater than average. However, wMPs do not have an equally important recognition in special invited roles in conferences. They are still under-represented in "Scientific Committees", "Invited Speakers", "Symposiums" and "Course directors". wMPs should be encouraged to participate even more actively in European conferences and the organizing committees should invite more wMPs in special roles. More studies concerning the status of female MPs in each country separately should be encouraged as they will help in understanding the position of wMPS in Europe.

Does clinical indication play a role in CT radiation dose in pediatric patients?

PURPOSE: The purpose of this study was to identify the main pathologies for which CT is applied on pediatric patients and the related radiation doses as reported in the literature in order to facilitate justification and CT optimization. METHODS: A critical analysis of a literature review was performed. Different search engines were used such as PubMed, Google Scholar and Science Direct. Various terms and keywords were used to locate pertinent articles such as Pediatric, Computed tomography, Radiation Dose, Organ dose, Effective dose. RESULTS: The results showed that the main pathologies for which CT is applied are: Crohn's disease, hydrocephalus, cystic fibrosis and pediatric malignancies-mainly lymphoma. The related radiation dose data are extremely scarce and are in the range of 3.48-17.56, 0.2-15.3mSv, 0.14-6.20mSv, and 2.8-518.0mSv, respectively. The radiation doses reported are high especially in pediatric oncology. CONCLUSIONS: Pediatric patients with malignancies are those exposed to the higher levels of radiation during CT imaging. Literature is lacking reporting of dose in Pediatric CT imaging. More studies need to be realized for the determination of radiation dose in those patients. Special protocols need to be recommended in order to reduce the exposure of children in radiation.

Hyperthermia Is Now Included in the NCCN Clinical Practice Guidelines for Breast Cancer Recurrences: An Analysis of Existing Data.

BACKGROUND: Hyperthermia has been included in the 2013 National Comprehensive Cancer Network (NCCN) guidelines as an option for the treatment of breast recurrences. The purpose of this article is to demonstrate the important role of hyperthermia as a therapeutic modality by presenting clinical trials on this subject carried out in the last decades. MATERIALS AND METHODS: All relevant trials published since 1987 were retrieved from Medline and reviewed. RESULTS: Results show that the addition of hyperthermia to radiotherapy and/or chemotherapy for the treatment of breast cancer enhances treatment response and can increase local control. CONCLUSION: Further studies are required to evaluate potential benefits of hyperthermia in the treatment of other kinds of superficial tumors.