BEGIN:VCALENDAR VERSION:2.0 PRODID:-//CERN//INDICO//EN BEGIN:VEVENT SUMMARY:PRRT as a tool for treatment of severe hypoglycemia in patients wi th primary inoperable insulinoma DTSTART;VALUE=DATE-TIME:20211011T091000Z DTEND;VALUE=DATE-TIME:20211011T093000Z DTSTAMP;VALUE=DATE-TIME:20260815T031129Z UID:indico-contribution-21-270@indico.koza.if.uj.edu.pl DESCRIPTION:Speakers: Marta Opalińska (Nuclear Medicine Unit\, Department of Endocrinology Department of Endocrinology\, Oncological Endocrinology and Nuclear Medicine\, University Hospital\, Kraków\, Poland)\nPRRT as a tool for treatment of severe hypoglycemia in patients with primary inopera ble insulinoma\n\nIntroduction\nSevere hypoglycaemia in a course of inoper able insulinoma may be life-threating and it is not always well controlled even by high doses of diazoxide\, which in some cases cause a significant toxicity. Nowadays\, other forms of effective therapy are not available - use of protein kinase inhibitors (everolimus\, sunitynib) sometimes bring satisfactory effect but is often associated with the risk of serious side effects. Use of Peptide receptor radionuclide therapy (PRRT) in patients with good expression of somatostatnin receptor\, characterized by relative ly low toxicity\, is potentially valuable treatment option.\n \nAim\nEvalu ation the PRRT effect on insulin levels in patients with primary inoperabl e insulinoma. \n\nMaterials and methods\n3 patients (female with metastati c insulinoma\, male with primary inoperable pancreatic tumor\, female with MEN1 syndrome and hepatic metastases) were treated with PRRT (90Y/177Lu D OTA-TATE or 90YDOTA-TATE in the dose 7.4GBq /m2) due to severe hypoglycemi a poorly controlled by diazoxide in course of primary inoperable insulinom a.\n\nResults\nIn all patients PRRT had no complications. Patient 1 baseli ne fasting glucose concentration increased to 5.9mmol/L from 2.4mmol/L aft er PRRT. In patient 2 fasting glucose level 2.30mmol/L[3.30 - 5.60] increa sed after PRRT to value 7.0mmol/L[3.30 - 5.60] while baseline insulin leve l initially 31.15uU/mL [2.6 - 24.9] dropped to 15.44uU/mL[2.6 - 24.9]. In patients 3\, baseline fasting glucose level 2.5mmol/L[3.30 - 5.60] increas ed after PRRT to value 7.9mmol/l[3.30 - 5.60]\, and insulin dropped from 5 7.96uU/mL[2.6 - 24.9] to 6.32 uU/mL[2.6 - 24.9]. 2 patients after PRRT had their dizaoxide dose reduced and 1 discontinued.\n\nConclusion\nPRTT was effective in reduction of serum insulin levels and diazoxide dose in patie nts with severe hypoglycaemia in the course of primary inoperable insulino ma.\n\nhttps://indico.koza.if.uj.edu.pl/event/4/contributions/270/ LOCATION:Theranostics Center / on-line URL:https://indico.koza.if.uj.edu.pl/event/4/contributions/270/ END:VEVENT BEGIN:VEVENT SUMMARY:Radioactive arsenic (III) compounds as potential theranostic radio pharmaceuticals DTSTART;VALUE=DATE-TIME:20211011T093000Z DTEND;VALUE=DATE-TIME:20211011T095000Z DTSTAMP;VALUE=DATE-TIME:20260815T031129Z UID:indico-contribution-21-247@indico.koza.if.uj.edu.pl DESCRIPTION:Speakers: Monika Łyczko (Institute of Nuclear Chemistry and T echnology)\nArsenic compounds have been known and used in medicine for cen turies. Arsenic (III) in the form of simple inorganic compounds easily oxi dizes\, which makes its administration in the human body difficult. As2O3 is now used in the successful treatment of acute promyelocytic leukemia. \ nThe high affinity of arsenic to sulfur atoms and creating strong bonds wi th sulfur-containing compounds provides a wide range of applications of ar senic compounds in medicine.\nThe application of arsenic compounds enables the use of a wide range of radioactive arsenic isotopes in nuclear medici ne\, both in diagnostics and therapy. Arsenic has four isotopes - β+ emit ters (70/71/72/74As) and three β- emitters (74/76/77As)\, which can be ob tained in a reactor or in an accelerator. The half-lives of As radioisotop es are in the range from 53 minutes to 18 days. 72As can be also obtained from the 72Se/72As generator [1\,2]\, which would facilitate the synthesis of radiopharmaceuticals in the hospital. Arsenic is also an interesting c andidate for use in the innovative β + γ diagnostic technique\, which al lows increasing the precision of the examination with the use of a lower d ose of the radioisotope for the patient [3].\nFor the synthesis of arsenic complexes on a weight scale the ligands containing thiol groups were used . The synthesis was carried out in a nitrogen atmosphere under reflux\, an d chloroform was used as a solvent. The four arsenic (III) compounds with dithiol ligands were obtained. The compounds were examined by X-ray diffra ction and their mass was determined by ESI Q-TOF-MS. The results of both s tudies confirmed the expected structure of the tested compounds\, which al lowed to determine the retention time of the peaks on HPLC chromatograms. Also\, the UV-Vis spectra of the tested complexes were measured. Toxicity studies of arsenic compounds on NB4 acute promyelocytic leukemia cells wer e performed using the MTS test. All compounds as well as As2O3 induced cyt otoxicity in a time and dose-dependent manner. \nThe established synthesis conditions on a weight scale allowed for the syntheses with the use of th e radioactive 76As isotope\, which were examined by TLC and HPLC methods. Radioactive complexes were formed with high efficiency within 0.5 h of syn thesis and were relatively stable in human serum.\n\nFunding: This work wa s supported by the IAEA Research Contract No: 23299 \n\n[1] E. Chajduk\, K . Doner\, H. Polkowska-Motrenko\, A. Bilewicz\, “Novel radiochemical sep aration of arsenic from selenium for 72Se/72As generator”\, Appl. Rad. I sot.\, vol. 70 pp. 819–822\, 2012.\n[2] M. Jennewein\, A. Schmidt\, A. F . Novgorodov\, S. M. Qaim\, F. Rösch\, “A no-carrier-added 72Se/72As ra dionuclide generator based on distillation”. Radiochim. Acta\, vol. 92\, pp. 245-249\, 2004.\n[3] M. Sitarz\, J.P. Cussonneau\, T. Matulewicz\, F. Haddad. “Radionuclide candidates for β+γ coincidence PET: An overview ”. Appl Radiat Isot. vol.155\, 108898\, 2020.\n\nhttps://indico.koza.if. uj.edu.pl/event/4/contributions/247/ LOCATION:Theranostics Center / on-line URL:https://indico.koza.if.uj.edu.pl/event/4/contributions/247/ END:VEVENT BEGIN:VEVENT SUMMARY:Quercetin loaded mesoporous silica nanoparticles to contrast gram positive and gram negative bacteria infections DTSTART;VALUE=DATE-TIME:20211011T103000Z DTEND;VALUE=DATE-TIME:20211011T105000Z DTSTAMP;VALUE=DATE-TIME:20260815T031129Z UID:indico-contribution-21-290@indico.koza.if.uj.edu.pl DESCRIPTION:Speakers: Cristina Carucci (University of Cagliari)\nNowadays antibiotic resistance is defined by the World Health Organization (WHO) as one of the biggest treat for human health. [1] In the absence of substant ial new antibiotic discovery\, drug delivery systems (DDS) can be used to transport and release a biologically active compound at the needed site. [ 2-3] Among several nanocarriers used for drug delivery\, mesoporous silica nanoparticles (MSNs) present several advantages. For example\, they prese nt an high surface area (up to 1000 m2/g) and they can be easily functiona lized with chemical groups which allow to increase\, delay\, and localize drug release at cell targets. [3] To date\, to increase MSNs biocompatibil ity and increase their stability polymer coated nanoparticles are under st udy. [4-5]\nIn this work\, MSNs were functionalized separately with two am ine groups\, triethylenetetramine (TETA) and 3-aminopropyltriethoxysilane (APTES) to give MSN-TETA and MSN-NH2 prior poly-L-lysine (PLL) modificatio n. After functionalization\, the flavonoid quercetin was loaded into MSNs. Structure and function were determined by a wide range of techniques such as TEM\, SAXS\, TGA\, FTIR\, N2-adsorption/desorption isotherms\, DLS and ELS. Drug release was assayed at different conditions (pH and drug loadin gs) giving release values within the range of drug concentration (2-10 µg /mL) in plasma after an oral administration dose of 200-500 mg of querceti n. Preliminary microbiological assays were also performed indicating a bet ter efficacy of the DDS against Gram positive bacteria. \n\nReferences\n[1 ] S. Hernando-Amado\, T.M. Coque\, F. Baquero\, Nat Microbiol\, 2019\, 4\, 1432–1442 \n[2] M. Vallet-Regí\, D\, Lonzano\, B. Gonzalez et al. Adva nced Healthcare Materials\, 2020\, 9\, 2000310 \n[3] RR. Castillo\, M. Val let-Regí\, Int J Nanomedicine\, 2021\;16:4409-4430\n[4] G.G. Abdo\, M.M. Zagho\, A.Khalil\, Emergent Materials\, 2020\, 3\, 407–425.\n[5] K. Kuld eep\,K.Deepak.\,A. Rosling\, J. Rosenholm\,Applied Science\, 2020\, 10\, 1 \, 289\n\nhttps://indico.koza.if.uj.edu.pl/event/4/contributions/290/ LOCATION:Theranostics Center / on-line URL:https://indico.koza.if.uj.edu.pl/event/4/contributions/290/ END:VEVENT BEGIN:VEVENT SUMMARY:193m\,195mPt-based nanobioconjugates for combined „chemo-Auger ” theranostics of hepatocellular carcinoma (HCC) and HER2+ breast cancer . DTSTART;VALUE=DATE-TIME:20211011T101000Z DTEND;VALUE=DATE-TIME:20211011T103000Z DTSTAMP;VALUE=DATE-TIME:20260815T031129Z UID:indico-contribution-21-246@indico.koza.if.uj.edu.pl DESCRIPTION:Speakers: Kamil Wawrowicz (Institute of Nuclear Chemistry and Technology\, Dorodna 16\, 03-195 Warsaw\, Poland)\nDespite the broad devel opment of medicine for cancer treatment\, current therapeutic approaches a re not efficient at dealing with aggressive and therapy-resistant neoplasm s such as breast cancer or hepatocellular carcinoma. In these tumors\, one of the most difficult steps of the therapy process is metastases treatmen t due to the spread of small size tumors. Targeted therapy with most effic ient Auger electrons emitters – 193mPt (30 A.E. per decay) and 195mPt (3 6 A.E. per decay) - is one of the most promising concept for this approach . Moreover\, 195mPt can be easily imaged via SPECT as a result of emission suitable for imaging photons with energy ~98.90 keV. Platinum-based radio pharmaceuticals\, due to their relevant characteristics\, are encouraging candidates for realizing “chemo-Auger” therapy which should be signifi cantly more effective than typical Auger therapy. Chemotoxicity of platinu m can be promoted in highly oxidative environment which occurs in most of hepatic cells and in some of breast/ovarian cancer cells. Biological effec tiveness studies of platinum-induced chemotoxicity were realized with two types of nanocarriers – 30 nm core-shell (Au@Pt) and ultra-small 2 nm pl atinum (PtNPs) nanoparticles\, used in forms of HER2+ targeted bioconjugat es with Trastuzumab\, as well as only polymer-stabilized conjugates for HC C. Research for non-radioactive (bio)conjugates chemotoxicity included eva luation for 2D and 3D in vitro tumor spheroid models. Moreover\, one of th e main parts was aimed at determining the mechanism of chemotoxicity. Ther e are two different concepts of platinum biological activity. In order to identify the factors responsible for cytotoxic effects\, nuclei isolation and oxidative stress markers determination were performed. Obtained result s confirmed\, that for chemotoxicity of platinum-based nanomaterials\, hig hly oxidative environment is a crucial parameter. Due to presence of natur ally occurring increased H2O2 concentration in HCC cells cytoplasm\, in th is cancer cells significant cytotoxicity was observed at similar level for both - Au@Pt and PtNPs conjugates (~50% at 72h post treatment). Furthermo re\, our results strongly indicates\, that in HER2 overexpressed breast/ov arian cancer cells the oxidative potential is insufficient for inducing cy totoxic effects of platinum. After widely conducted chemical and biologica l research for non-radioactive conjugates\, evaluation with radioactive 19 3m\,195mPt will be performed. Due to very limited availability of high spe cific activity Pt radionuclides\, during subsequent part of research\, var ious direct and indirect ways for high specific activities production will be under investigation.\nThis research was funded by National Science Cen tre (NCN)\, grant number UMO-2019/35/B/ST4/01433 (OPUS)”. The contributi on of PhD student Kamil Wawrowicz was realized within Project No. POWR.03. 02.00-00-I009/17-00 (Operational Project Knowledge Education Development 2 014–2020 co-financed by European Social Fund).\n\nhttps://indico.koza.if .uj.edu.pl/event/4/contributions/246/ LOCATION:Theranostics Center / on-line URL:https://indico.koza.if.uj.edu.pl/event/4/contributions/246/ END:VEVENT BEGIN:VEVENT SUMMARY:Novel and fast method of gene mutation identification using Surfac e Enhanced Raman Spectroscopy (SERS) DTSTART;VALUE=DATE-TIME:20211011T095000Z DTEND;VALUE=DATE-TIME:20211011T101000Z DTSTAMP;VALUE=DATE-TIME:20260815T031129Z UID:indico-contribution-21-245@indico.koza.if.uj.edu.pl DESCRIPTION:Speakers: Jan Krajczewski (Faculty of Chemistry\, University o f Warsaw)\nAn early and accurate diagnosis of specific DNA mutations has a decisive role for effective treatment. Especially\, when an immediate dec ision on treatment most needs to be made\, the rapid and precise confirmat ion of clinical findings is vital. Herein\, we show a new strategy for the gene mutation (BRAF c.1799T>A\; p. V600E) identification using highly SER S-active and reproducible SERS substrate (photo-etched GaN covered with a thin layer of sputtered gold) and surface enhanced Raman scattering (SERS) spectroscopy. The detection is based on the conformation change (gauche → trans) of the alkanethiol linker modifying the capture DNA during the hybridization process. The value of the intensity ratio of the ν(C–S) b ands of the trans and gauche conformer higher than 1.0 indicated the prese nce of mutation. The demonstrated new DNA SERS (bio)sensor is characterize d by the low detection limit at the level of pg/μL\, wide analytical rang e from 6.75 pg/μL to 67.5 ng/μL and high selectivity. The proposed b ioactive platforms\, based on nanostructured GaN substrates modified with thiolated ssDNA (single stranded DNA) can be successfully used in the anal ysis of clinical samples.\n\nhttps://indico.koza.if.uj.edu.pl/event/4/cont ributions/245/ LOCATION:Theranostics Center / on-line URL:https://indico.koza.if.uj.edu.pl/event/4/contributions/245/ END:VEVENT END:VCALENDAR