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1

Towards high sensitivity and high-resolution PET scanners: imaging-guided proton therapy and total body imaging

Lang Karol

Bio-Algorithms and Med-Systems

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2022

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Vol. 18, no. 1

96--106

EN

Quantitative imaging (i.e., providing not just an image but also the related data) guidance in proton radiation therapy to achieve and monitor the precision of planned radiation energy deposition field in-vivo (a.k.a. proton range verification) is one of the most underinvested aspects of radiation cancer treatment despite that it may dramatically enhance the treatment accuracy and lower the exposure related toxicity improving the entire outcome of cancer therapy. In this article, we briefly describe the effort of the TPPT Consortium (a collaborative effort of groups from the University of Texas and Portugal) on building a time-of-flight positronemission-tomography (PET) scanner to be used in preclinical studies for proton therapy at MD Anderson Proton Center in Houston. We also discuss some related ideas towards improving and expanding the use of PET detectors, including the total body imaging.

2

Prospects for the production of radioisotopes and radiobioconjugates for theranostics

Choiński Jarosław, Łyczko Monika

Bio-Algorithms and Med-Systems

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2021

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Vol. 17, no. 4

241--257

EN

The development of diagnostic methods in medicine as well as the progress in the synthesis of biologically active compounds allows the use of selected radioisotopes for the simultaneous diagnosis and treatment of diseases, especially cancerous ones, in patients. This approach is called theranostic. This review article includes chemical and physical characterization of chosen theranostic radioisotopes and their compounds that are or could be useful in nuclear medicine.

3

Specjacja cyny w preparatach radiofarmaceutycznych - czynniki wpływające na wyniki oznaczeń Sn (II)

Staniszewska Joanna, Korytkowski Michał, Korsak Agnieszka

Analityka : nauka i praktyka

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2021

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nr 1

34--38

PL

Mając na celu zapewnienie jakości wyników oznaczania czynnika redukującego w kontroli jakości zestawów, podjęto badania porównawcze wody oczyszczonej, pochodzącej z różnych źródeł. Badania miały na celu sprawdzenie wpływu sposobu oczyszczenia wody na zawartość nieidentyfikowanych i niespecyfikowanych substancji organicznych i nieorganicznych o właściwościach utleniających, a następnie wybranie wody o stopniu czystości odpowiednim do zastosowania w analizie cyny(II).

4

Zastosowanie związków kompleksowych rutenu, złota, wanadu, chromu, bizmutu, technetu w medycynie. Cz. 2

Pawlak Marta, Drzeżdżon Joanna, Jacewicz Dagmara

Wiadomości Chemiczne

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2020

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[Z] 74, 11-12

823--851

EN

In this review, the most important complex compounds of ruthenium, gold, vanadium, chromium, bismuth, technetium were selected, and then their most important applications were described in medicine. Ruthenium has been identified as a metal with potential medical use, useful in cancer chemotherapy. The possibility of using its chemical behavior by developing complexes activated for cytotoxic activity through a mechanism of reduction in tumor tissue was discovered. Among the new anti-cancer drugs based on complex compounds, gold compounds have gained a lot of interest. This is due to their strong inhibitory effect on the growth of cancer cells and the observation that many compounds inhibit the enzyme thioredoxin reductase. This enzyme is important for the proliferation of cancerous tissues, and its inhibition is associated with the release of anti-mitochondrial effects. Clinical tests have shown that vanadium compounds can be used as anti-diabetic drugs with low toxicity. However, the therapeutic concentration range is very narrow, just a few micromoles of the compound are enough to cause apoptosis, necrosis and inflammation of healthy cells. Chromium improves the glucose system in people with hypoglycemia or hyperglycemia. Vanadium compounds mainly used to create potential drugs are inorganic compounds such as vanadates(V), vanadyl cation(IV), vanadium oxide(V) and a number of compounds containing organic ligands. Among the metal complexes, chromium(III) picolinate has successfully become a nutrient used to prevent high blood sugar levels. One of the most commonly used bismuth(III) compounds is bismuth subsalicylate. It is one of the few bismuth compounds regularly used to treat various gastrointestinal complaints, including duodenal ulcers. 99mTc injected into the body, depending on its chemical form and molecular structure, concentrates in the examined organ and emits a quantum that allows imaging of the organ through flat scintigraphic or emission processes. The role of complex compounds in medical imaging is largely based on the creation of radiopharmaceuticals for early detection of diseases and cancer radiotherapy. Radiopharmaceuticals are radionuclide-containing drugs and are routinely used in nuclear medicine to diagnose or treat a variety of diseases.

5

Pochodne L-tyrozyny jako leki oraz znaczniki do obrazowania nowotworów

Pająk Małgorzata

Przemysł Chemiczny

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2020

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T. 99, nr 10

1541--1545

PL

L-Tyrozyna jest prekursorem związków biologicznie aktywnych, a jej zaburzony metabolizm prowadzi do wielu schorzeń, w tym do choroby Parkinsona i albinizmu. W ostatnim czasie wzrosło zainteresowanie syntezą znakowanych izotopowo halogenowych i metylowych pochodnych tego aminokwasu o potencjalnym zastosowaniu w medycynie nuklearnej. Przed wprowadzeniem nowego związku do organizmu chorego ważne jest, aby prześledzić jego wpływ na reakcje szlaku metabolicznego L-tyrozyny. Dokonano przeglądu obecnie stosowanych radiofarmaceutyków, będących pochodnymi L-tyrozyny, oraz omówiono ich wpływ na reakcje enzymatyczne, w których bierze udział ten aminokwas.

EN

A review, with 41 refs., of currently used radiopharmaceuticals and particularly of labeled halogenated and methylated derivatives of L-tyrosine used as potential radiotracers for nuclear medicine.

6

Radiofarmaceutyki w Instytucie Chemii i Techniki Jądrowej

Walczak R., Halik P., Gawęda W., Dziawer Ł., Gumiela M.

Postępy Techniki Jądrowej

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2018

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z. 2

41--47

PL

Instytut Chemii i Techniki Jądrowej jest jedną z nielicznych placówek w Polsce, w których prowadzone są badania nad otrzymywaniem nowych radiofarmaceutyków. Prace w tym zakresie prowadzi Pracownia Badań i Syntezy Radiofarmaceutyków pod kierownictwem prof. dr hab. Aleksandra Bilewicza. Tematyka prowadzonych badań jest ukierunkowana na opracowanie nowych metod produkcji radionuklidów oraz sposobów ich dostarczania do miejsc zmian patologicznych w organizmie człowieka. W artykule przedstawiono opisy badań realizowanych przez doktorantów tej Pracowni w ramach prac doktorskich. Wśród tych prac należy wymienić nanonośniki dla emiterów promieniowania alfa, badania nad inhibitorami cholinoesteraz, nowe metody wytwarzania 99mTc i 43Sc czy produkcję radiofarmaceutyków teranostycznych.

EN

The Institute of Nuclear Chemistry and Technology is one of the few institutions in Poland, where research on the acquisition of new radiopharmaceuticals is being conducted. The work in this area is carried out by the Laboratory of Research and Synthesis of Radiopharmaceuticals under the supervision of prof. dr hab. Aleksander Bilewicz. The research is focused on the development of new methods of radionuclide production and methods of their delivery to pathological changes in the human body. The article presents descriptions of research carried out by doctoral students as part of their theses. These include the nanocarriers for alpha-emitters, the study of cholinesterase inhibitors, new methods for the production of 99mTc and 43Sc, as well as the production of teranostatic radiopharmaceuticals.

7

Imaging of hypoxia in small animals with 18F fluoromisonidasole

Kilian K., Rogulski Z., Cheda Ł., Drzał A., Gerszewska M., Cudny M., Elas M.

Nukleonika

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2016

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Vol. 61, No. 2

119--223

EN

A method of automated synthesis of [18F]fluoromisonidazole ([18F]FMISO) for application in preclinical studies on small animals was presented. A remote-controlled synthesizer Synthra RNplus was used for nucleophilic substitution of NITTP (1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonyl-propanediol) with 18F anion. Labeling of 5 mg of precursor was performed in anhydrous acetonitrile at 100°C for 10 min, and the hydrolysis with HCl was performed at 100°C for 5 min. Final purifi cation was done with high-performance liquid chromatography (HPLC) and the radiochemical purity of radiotracer was higher than 99%. Proposed [18F]FMISO synthesis was used as a reliable tool in studies on hypoxia in Lewis lung carcinoma (LLC) in mouse models.

8

Radiofarmaceutyki w nowoczesnych technikach diagnostyki obrazowej, cz. I - obrazowanie medyczne

Pęgier M., Pęgier M., Kilian K., Pyrzyńska K.

Analityka : nauka i praktyka

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2015

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nr 1

44--49

PL

Radiofarmaceutyki pozwalają na obrazowanie wielu procesów w organizmie, dzięki czemu mogą służyć do diagnostyki rozmaitych stanów patologicznych.

9

Radiofarmaceutyki w nowoczesnych technikach diagnostyki obrazowej, cz. II - synteza i kontrola jakości radiofarmaceutyków do tomografii pozytonowej

Pęgier M., Pęgier M., Kilian K., Pyrzyńska K.

Analityka : nauka i praktyka

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2015

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nr 2

16--23

PL

Pozytonowa tomografia emisyjna (PET) jest dynamicznie rozwijającą się techniką obrazowania medycznego. Wykorzystuje się w niej radiofarmaceutyki, stanowiące połączenie radioizotopu oraz liganda odpowiedzialnego za transport nuklidu i włączenie go w odpowiedni proces w organizmie.

10

Radiofarmaceutyki : aspekty kontroli jakości zawartości substancji czynnej na przykładzie kwasu metylenodifosfonowego (MDP)

Staniszewska J., Bulska E.

Analityka : nauka i praktyka

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2013

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nr 4

4--10

PL

Właściwie prowadzona kontrola jakości radiofarmaceutyków gwarantuje bezpieczeństwo ich stosowania do celów medycznych, stąd tak wiele uwagi poświęca się opracowywaniu i walidacji stosowanych do tego celu procedur pomiarowych-.

11

Production of 18F by proton irradiation of C6H6NF and C6H5NF2

Běták E., Mikołajczak R., Staniszewska J., Mikołajewski S., Rurarz E., Wojtkowska J.

Nukleonika

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2011

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Vol. 56, No. 4

269-276

EN

Fluorin--18 can be produced directly by the (p,pn) reaction and also indirectly by the (p,2n) reaction on the 19F target. The overall cross section for both routes is 108 plus or minus 20 mb at 22.5 plus or minus 2.5 MeV. In this work, we obtained 18F, using 25 MeV protons on 2\--fluoroaniline and 2,4-difluoroaniline targets. The chemical separation yield was 46 š 7% and 47 plus or minus 12% for 2-fluoroaniline and 2,4-difluoroaniline, respectively. Low-current 1 h irradiations led to 90 mi Ci of 18F produced from 2-fluoroaniline bombarded with a 70 nA beam (in good agreement with the theoretical value, 96 mi Ci) and to 76 mi Ci of 18F in case of 2,4-difluoroaniline and a 33 nA beam (prediction 85 mi Ci). Both values are close to the thick target result reported by Dmitriev and Molin [4] for 22 MeV protons.

12

Enriched water-H2 18 O purification to be used in routine 18FDG production

Al Rayyes A. H.

Nukleonika

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2010

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Vol. 55, No. 3

401-405

EN

18O-water obtained from an 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG, Synthera) synthesis unit is used for purification. The purification process consists of ultraviolet (UV) irradiation followed by a distillation in a preevacuated system. After purification, the loss of enriched water was about only 5 per cent. Organic compounds, radioisotopes, trace metals and gases are eliminated efficiently. Results show that there is no significant difference in the production yield of 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) whether using purified enriched water by the proposed method of purification or using the new enriched water. This method offers the necessary precaution from contamination by tritium during the purification process. The obtained 18FDG or Na-18F using the purified 18O-water is of tritium free.

13

Metody kontroli jakości radiofarmaceutyków i promieniotwórczych związków chemicznych stosowanych w medycynie

Staniszewska J., Bulska E.

Analityka : nauka i praktyka

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2008

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nr 1

51-54

14

Production of [103Pd]Bleomycin complex for targeted therapy

Jalilian A., Yari-Kamrani Y., Sadeghi M.

Nukleonika

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2006

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Vol. 51, nr 2

119-123

EN

Due to the anticancer properties of bleomycin (BLM) complexes, production of [103Pd]bleomycin ([103Pd]BLM) was targeted. Palladium-103 (T1/2 = 16.96 d) was produced via the 103Rh(p,n)103Pd nuclear reaction using a natural rhodium target. Proton energy was 18 MeV with 200 mA irradiation for 15 h (final activity 25.9 GBq of 103Pd2+, RCP > 95%, radionuclidic purity > 99%). 103Pd was separated from the irradiated target by anion exchange using a Dowex 1´8 (Cl-)/100-200 mesh resin in the form of Pd(NH3)2Cl2 in order to react with bleomycin to yield [103Pd]BLM. Chemical purity of the final product was in accordance to the accepted limits. [103Pd]BLM was prepared with a radiochemical yield of more than 98% at 80°C in 30 min. The labeling reaction was optimized for time, temperature and ligand concentration. Radiochemical purity of more than 99% was obtained using RTLC with specific activity of about 370 MBq/mmol. The stability of the tracer was checked in the final product and presence of human serum at up to 3 h. The complex was stable in human serum at 37°C up to 2 h of incubation. Biodistribution studies using a SPECT system performed in normal rats in the first 2-3 h.

15

Preparation of [61Cu]DTPA complex as a possible PET tracer

Jalilian A., Rowshanfarzad P., Sabet M., Kamalidehghan M.

Nukleonika

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2006

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Vol. 51, nr 2

111-117

EN

Copper-61 (T1/2 = 3.33 h) produced via the 64Zn(p,alfa)61Cu nuclear reaction, using a natural zinc target, was separated from the irradiated target material by two ion exchange chromatography steps and was used for the preparation of [61Cu]-diethylenetriaminepentacetate ([61Cu]DTPA) using freshly-prepared DTPA cyclic dianhydride. An electroplated natural zinc layer on a gold-coated copper backing was irradiated with 22 MeV protons (22 12 MeV on the target, 180 miA irradiation, 3.2 h, final activity 220 GBq of 61Cu2+, RCY > 95%, radionuclidic purity > 99%, 60Cu as the only radionuclidic impurity; T1/2 = 23.7 min). Colorimetric methods showed that traces of chemical impurities in the product were below the accepted limits. The solution of [61Cu]DTPA was prepared with a radiochemical yield of more than 80% starting with 61CuOAc ligand at room temperature after 30 min. RTLC showed the radiochemical purity of more than 99%. The specific activity obtained was about 9.1 TBq/mmol. The tracer was shown to be stable in the final product and in the presence of human serum at 37°C up to 3 h.

16

Preparation and biodistribution of [201Tl](III)vancomycin complex in normal rats

Jalilian A., Hosseini M., Karimian A., Saddadi F., Sadeghi M.

Nukleonika

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2006

|

Vol. 51, nr 4

203-208

EN

Thallium-201 (T1/2 = 3.04 days) in Tl+ form was converted to Tl3+ cation in presence of O3 in 6 M HCl controlled by RTLC/gel electrophoresis methods. The final evaporated activity was reacted with vancomycin (VAN) in water to yield [201Tl](III)VAN. The best results were obtained at room temperature in water after 30 min with a radiochemical yield > 99%, after mixing the reactants followed by SPE purification using Si Sep-Pak. The studies showed that thallic ion is mostly incorporated into vancomycin with a radiochemical purity of more than 98 š 1% by RTLC. A specific activity of about 4.14 x 1010 Bq/mmol was obtained. Radiochemical purity and stability of 201Tl-VAN in the preparation and in presence of human serum was determined up to 5.5 days. Biodistribution study of 201Tl(III)-vancomycin in normal rats was performed up to 52 h.

17

Radioisotopes for medical and industrial use during the 50-year history of the Institute of Nuclear Research

Mikołajczak R., Bazaniak Z., Iller E.

Nukleonika

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2005

|

Vol. 50,suppl.3

83-87

EN

The paper summarises the 50-years long history of the development of research programmes related to the practical applications of radionuclides in various fields of the Polish economy. The changing trends of interest of the potential users are reflected in the research and development activities of the Radioisotope Centre POLATOM. In the 1960's and 1970's the main areas of activity were focused on the sealed sources and radiolabelled compounds for the investigation of industrial processes. The introduction to the routine practice of the RIA and the IRMA kits for hormonal in vitro diagnostics in the 70-ties and 80-ties resulted in the general availability of this diagnostic technique in Poland. The number of radioisotopes having the required radiation type, energy and half-life is steadily increasing due to the progress in irradiation facilities and in chemical separation processes. The need for modern radiopharmaceuticals, more specific and providing higher diagnostic and therapeutic potential as an alternative to other medical modalities is reflected in the research programmes carried out and implemented currently at the Radioisotope Centre POLATOM.

18

Development of 111In-DTPA-human polyclonal antibody complex for long-term inflammation/infection detection

Jalilian A., Rowshanfarzad P., Shafaii K., Kamali-Dehghan M., Moafian J., Akhlaghi M., Babaii M., Rajabifar S., Mirzaii M.

Nukleonika

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2005

|

Vol. 50, nr 3

91-96

EN

Human polyclonal antibody (HIgG) was successively labeled with 111In-indium chloride after residulation with freshly prepared cyclic DTPA-dianhydride. The best results of the conjugation were obtained by the addition of solid DTPA-dianhydride (0.1 0.3 mg) to 100 mi l of the HIgG solution (0.2 0.4 mg/ml) at pH = 6 in phosphate buffer media at 25°C with continuous stirring for 30 min. Radio-thin-layer chromatography showed an overall radiochemical yield of 96 99% at optimized conditions (specific activity = 300 500 MBq/mg, radiochemical purity >98%). The final isotonic 111In-DTPA-HIgG complex was checked by radio-TLC to ensure the formation of only one species followed by filtration through a 0.22 mi filter. Preliminary long-term in vivo studies in turpentine-oil induced inflammation in rat model was performed to determine late complex distribution of the radioimmunoconjugate. The target/skin and target/ blood ratios were 27 and 51 after 24 h, and 23 and 51 after 110 h, showing a high selectivity of the radiopharmaceutical for inflammatory lesions.

19

Nowe technologie dla produkcji radiofarmaceutyków i materiałów medycznych

Bazaniak Z., Iller E., Mikołajczak R.

Przemysł Chemiczny

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2003

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T. 82, nr 8-9

1273-1274

20

The use of electronic autoradiography in nuclear medicine

Samochocka K., Rysińska A., Kozłowicz-Gudzińska I.

Nukleonika

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1998

|

Vol. 43, nr 4

435-438

EN

The use of Instant Imager (Canberra Packard), Microchannel Plate Analysers in Nuclear Medicine for a quality control of radiopharmaceuticals and for a pharmaceutical biodistribution study research is described. The suitability of the electronic autoradiography (EA) system has been verified for (sup 67)Ga, (sup 131)I and (sup 99m)Tc.

PL

Opisano zastosowanie mikrokanalikowego detektora, Instant Imager, firmy Canberra Packard, w medycynie nuklearnej do kontroli jakości radiofarmaceutyków oraz ich biodystrybucji. Użyteczność układu tzw. elektronicznej autoradiografii (EA) została sprawdzona dla radionuklidów: (sup 67)Ga, (sup 131)I, (sup 99m)Tc.