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1

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.

2

Assessment of the staff absorbed dose related to cyclotron operation and service in the production of 18F radiopharmaceuticals

Sadat-Eshkevar S. M., Karimian A., Mirzaii M.

Nukleonika

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2012

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Vol. 57, No. 3

407-410

EN

Cyclotron accelerators are used to produce medical radioisotopes. One of the most important problems which may be encountered is malfunction of a part of the target or beam line which requires stopping of the bombardment and making a repair. The decision about doing the repair depends on the whole body dose rate in a target room. In this work, dosimetric conditions related to the production of 18FDG radiopharmaceutical were simulated by the Monte Carlo (MC) method. Independently, the dose rates were measured by 7 ICRU spherical body phantoms placed inside the liquid target room and the maze of the cyclotron. The radiation dose rate inside the target room depends on the duration of the bombardment and the time passed after stopping the bombardment. The correlation between duration of the bombardment and required time after stopping the bombardment to reach the absorbed dose rate less than 25 mi Sv/h, was calculated for the presence and absence of the irradiated target. The results showed that the repair can be started immediately after stopping of the proton bombardment only if the target has been ejected from the target room and the duration of bombardment has not taken more than 10 min.

3

Obrazowanie struktury i czynności narządów wewnętrznych metodą PET : podstawy fizyczne

Królicki L., Bajera A., Kunikowska J.

Inżynier i Fizyk Medyczny

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2012

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Vol. 1, nr 2

39--43

PL

Technika PET jest obecnie podstawową metodą obrazowania molekularnego. Jest stosowana w diagnostyce, określeniu stopnia zaawansowania choroby oraz w monitorowaniu leczenia. Do podstawowych rozwiązań, które jednoznacznie przyczyniły się do rozwoju techniki PET należą wprowadzenie iteracyjnych metod rekonstrukcji obrazów, zastosowanie nowych typów kryształów scyntylacyjnych, wprowadzenie metody PET-CT, opracowanie metody time of flight, a obecnie zastosowanie metody PET-MRI. Zrozumienie zasad techniki PET, jej zalet, a przede wszystkim ograniczeń, jest niezbędne nie tylko dla właściwej interpretacji ostatecznego wyniku przez lekarza, ale również dla optymalizacji parametrów skanowania i oceny źródeł artefaktów przez fizyka/ inżyniera medycznego.

EN

At present, PET is a basic method of molecular imaging. It is applied in diagnostics, for determining the degree of the progress of illness and in monitoring the treatment. To basic answers which explicitly contributed to the development of PET belong introduction of iterative methods for reconstruction of images, applying new types of scintillators, implementing the hybrid PET-CT scanners, developing the method time of flight, and at present, application of PETMRI. Understanding principles of the technique, its limitations and advantages, is essential not only for appropriate interpretation of the final result by the doctor, but especially for the optimization parameters of scanning and the evaluation of sources of artifacts by the medical physics/engineer.

4

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.

5

Cyclotron production of 68Ga via proton-induced reaction on 68Zn target

Sadeghi M., Kakavand T., Rajabifar S., Mokhtari L., Rahimi-Nezhad A.

Nukleonika

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2009

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Vol. 54, No. 1

25-28

EN

68Ga is an important positron-emitting radionuclide for positron emission tomography. In this work 68Ga was produced via the 68Zn(p,n)68Ga nuclear reaction. 68Zn electrodeposition on a copper substrate was carried out by alkaline cyanide baths. 68Zn target was irradiated with a 15 MeV proton beam and a 150 mi A current. The production yield achieved was 136 mCi/ mi Aźh (5.032 GBq/mi Aźh). 68Ga was separated from zinc and copper by a combination of cation exchange chromatography and liquid-liquid extraction methods.

6

Wpływ zawartości gazów resztkowych na parametry pracy cyklotronu AlC-144

Sulikowski J., Guguła K., Daniel K., Sroka A., Marszałek K.

Elektronika : konstrukcje, technologie, zastosowania

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2009

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Vol. 50, nr 1

74-76

PL

Cyklotron AlC-144 znajdujący się w Instytucie Fizyki Jądrowej jest przeznaczony głównie do celów medycznych, tzn. do protonowej terapii oka [1]. Terapia wymaga wytworzenia przez cyklotron wiązki przyspieszonych protonów o stabilnych parametrach [2]. W szczególności pożądana jest stabilność wiązki protonów, powtarzalność parametrów wiązki i niezawodność pracy cyklotronu. W skład gazów resztkowych w komorze cyklotronu wchodzą: gazy przedostające się przez nieszczelności rzeczywiste komory z atmosfery otaczającej cyklotron, gazy desorbowane ze ścian komory i elementów jej wyposażenia, pary olejów pomp dyfuzyjnych i niezjonizowane gazy wypływające ze źródła jonów. W niniejszej pracy przedstawiono wpływ zawartości gazów resztkowych w komorze cyklotronu na niektóre parametry pracy cyklotronu. Przedstawiono w niej zależność czystości gazów w źródle protonów na stabilność i niezawodność pracy źródła, oraz wpływ zawartości gazów resztkowych w komorze na działanie elementów pracujących pod wysokim napięciem: układu przyspieszania i układu wyprowadzania wiązki protonów poza komorę cyklotronu [3].

EN

AlC-144 cyclotron operating in Institute of Nuclear Physics is dedicated to medical applications, mainly proton therapy of occular melanoma [1]. This type of medical treatment requires accelerated ion beam with stable parameters [2]. The most important are stability of proton beam, reproducibility of beam parameters and reliability of cyclotron work. Residual gases inside the cyclotron chamber are coming from leaks, desorption, contamination of oil diffusion pumps and ion source. The paper presents the influence of residual gases in cyclotron chamber on work parameters of the cyclotron. The discussion concerns the influence of purity of gas in proton source on stability of source parameters and residual gas content on high voltage element work: accelerating and ion beam deflecting systems [3].

7

The proton beam energy measurement by a time-of-flight method

Kisieliński M., Wojtkowska J.

Nukleonika

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2007

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Vol. 52, nr 1

3-5

EN

A simple TOF equipment for cyclotron protons beam energy measurement was constructed. For short distance of 165 cm between capacitive pick-up probes, the accuracy of proton beam energy is below 1% for mean beam currents above 200 nA and within the energy range 20 30 MeV.

8

Simulation of operation modes of isochronous cyclotron by a new interative method

Taraszkiewicz R., Talach M., Sulikowski J., Doruch H., Norys T., Sroka A., Kiyan I.

Nukleonika

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2007

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Vol. 52, nr 1

29-34

EN

Operation mode simulation methods are based on selection of trim coil currents in the isochronous cyclotron for formation of the required magnetic field at a certain level of the main coil current. The traditional current selection method is based on finding a solution for all trim coils simultaneously. After setting the calculated operation mode, it is usually necessary to perform a control measurement of the magnetic field map and to repeat the calculation for a more accurate solution. The new current selection method is based on successively finding solutions for each particular trim coil. The trim coils are taken one by one in reverse order from the edge to the center of the isochronous cyclotron. The new operation mode simulation method is based on the new current selection method. The new method, as against the traditional one, includes iterative calculation of the kinetic energy at the extraction radius. A series of experiments on proton beam formation within the range of working acceleration radii at extraction energies from 32 to 59 MeV, which were carried out at the AIC144 multipurpose isochronous cyclotron (designed mainly for the eye melanoma treatment and production of radioisotopes) at the INP PAS (Kraków), showed that the new method makes unnecessary any control measurements of magnetic fields for getting the desired operation mode, which indicates a high accuracy of the calculation.

9

Preparation and biodistribution of [67Ga]-insulin for SPECT purposes

Jalilian A. R., Garousi J., Gholami E., Akhlaghi M., Bolourinovin, Rajabifar S.

Nukleonika

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2007

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Vol. 52, nr 4

145-151

EN

Human recombinant insulin was successively labeled with [67Ga]-gallium chloride after conjugation with freshly prepared cyclic DTPA-dianhydride (ccDTPA). The best results of the conjugation were obtained by the addition of 0.5 ml of an insulin pharmaceutical solution (5 mg/ml, in phosphate buffer, pH = 8) to a glass tube precoated with DTPA-dianhydride (0.01 mg) at 25°C with continuous mild stirring for 30 min. Radiothin-layer chromatography (RTLC), instant thin-layer chromatography (ITLC) and high-performance liquid chromatography (HPLC) showed overall radiochemical purity higher than 96% in optimized conditions (specific activity = 300 500 MBq/mg, labeling efficiency 77%). Preliminary in vivo studies with normal rats were performed to determine the biodistribution of the radiotracer up to 110 h. They showed a high liver uptake of the tracer which is consistent with other reported radiolabeled insulins.

10

Production, quality control and initial imaging studies of [82mRb]RbCl for PET studies

Rowshanfarzad P., Jalilian A., Kiyomarsi M., Sabet M., Karimian A., Moradkhani S., Mirzaii M.

Nukleonika

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2006

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Vol. 51, nr 4

209-215

EN

Rubidium-82m was prepared via 15.4 MeV proton irradiation of a krypton-82 gaseous target (30% enrichment). Washing the target chamber with hot water yielded a Rb-82m containing solution, which was further purified using short column chromatography in order to remove organic/inorganic impurities. The flowthrough was formulated in normal saline for injection. Radionuclide, radiochemical and chemical purity tests were performed prior to administration to rats for imaging (radiochemical yield: 95-97%, radiochemical purity > 97%). Preliminary dual-head coincidence studies were performed to determine the distribution of [82mRb]Rb in normal rats. For biodistribution studies, Rb-81 was injected to rats and tracer accumulation in heart, GI and bladder was determined after sacrification in time intervals. A yield of 1.3 GBq at EOB, 235.7 MBq/mAh was obtained.

11

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.

12

Production and separation of manganese-54 from alpha-irradiated V2O5 target

Kłos M., Bartyzel M., Petelenz B.

Nukleonika

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2006

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Vol. 51, nr 4

221-224

EN

Our aim was to obtain and isolate the carrier-free gamma emitter, 54Mn. Manganese-54 was produced via cyclotron activation in the 51V(alfa,n)54Mn reaction, and separated from HCl solution on Dowex-50 . 8 resin. The effectiveness of chemical separation was checked using the internal tracer 48V, produced in a cyclotron via the natTi(p,xn)48V reaction. The microcomponent 54Mn was eluted from the column with 3 M HCl, and vanadium with a 0.1 M HCl/ethanol/H2O2 mixture. The pair Ti/48V was separated on Dowex-50 . 8, using 0.03 M HClO4 as the eluent for 48V and 1 M HClO4 for natTi. The carrier-free 54Mn was of 99.9% radionuclide purity. In separation of the carrierfree pair 54Mn/48V, the recovery yield was 98.7% for 54Mn and 96.4% for 48V.

13

Production and quality control of 66Ga radionuclide

Sabet M., Rowshanfarzad P., Jalilian A., Ensaf M., Rajamand A.

Nukleonika

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2006

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Vol. 51, nr 3

147-154

EN

The purpose of this study was to develop the required targetry and radiochemical methods for production of 66Ga, according to its increasing applications in various fields of science. The 66Zn(p,n)66Ga reaction was selected as the best choice for the production of 66Ga. The targets were bombarded with 15 MeV protons from cyclotron (IBA-Cyclone 30) at the Nuclear Research Center for Agriculture and Medicine (NRCAM) with a current of 180 mA for 67 min. ALICE and SRIM (Stopping and Range of Ions in Matter) nuclear codes were used to predict the optimum energy and target thickness. Targets were prepared by electroplating 95.73% enriched 66Zn on a copper backing. Chemical processing was performed by a no-carrier-added method consisting of ion exchange chromatography and liquid-liquid extraction. Anion exchange chromatography was also used for the recovery of target material. Quality control of the product was carried out in two steps of chemical and radionuclide purity control. The activity of 66Ga was 82.12 GBq at EOB and the production yield was 410.6 MBq/mAh. The radiochemical separation yield was 93% and the yield of chemical recovery of the target material was 97%. Quality control tests showed a radionuclide purity higher than 97% and the amounts of chemical impurities were in accordance with the United States Pharmacopoeiae levels.

14

Production and quality control of 65Zn radionuclide

Rowshanfarzad P., Jalilian A., Sabet M.

Nukleonika

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2005

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Vol. 50, nr 3

97-103

EN

Zinc-65 was produced in the Nuclear Research Center for Agriculture and Medicine (NRCAM) by the bombardment of natural copper targets with 30 MeV protons via the 65Cu(p,n)65Zn nuclear reaction. Natural copper was used instead of enriched 65Cu because of the quick decay of undesired radioisotopes. It was also more desirable for cost effectiveness. Cross-section calculations were performed by ALICE nuclear code and the results were compared with the experimental data given in the literature, which showed good agreement. A 160 mi m copper layer target was bombarded with a 150 miA current of 30 MeV protons for 20 min, which resulted in 170 MBq activity of 65Zn product. The yield was 3.4 MBq/miAh. The concentration of the product was 6.8 MBq/ml. Radiochemical separation was carried out by anion exchange chromatography with the yield of about 98%. Quality control of the final product showed a radionuclide purity of more than 98% and no traces of possible impurities (copper) were detected by a colorimetric method with a 1 ppm detection limit using dithizone as the reagent. The materials used for targetry and chemical separation were quite cost-effective.

15

World trends in cyclotron developments for nuclear physics and applications

Baron E.

Nukleonika

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2003

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Vol. 48,suppl.2

3-11

EN

Today, the number of cyclotrons operating in the world largely exceeds 200. The field of uses covers production of radioisotopes for medicine, therapy by neutron and ion beams, nuclear, atomic and solid state physics research, material analysis and radiation damage studies, and production of intense neutron beams for present and future purposes. Despite this diversity, continuing efforts driven by both research laboratories as well as commercial firms result in a series of improvements in the various techniques used in the design and operation of cyclotrons. This paper intends to draw the main directions of evolution in the following issues: injection and extraction systems, beam dynamics (including high intensity issues), magnetic and electric fields computation, as well as existing and possible future applications in medicine, production of energy, neutron spallation sources and transmutation technologies. The question of a possible resurrection of FFAG (Fixed-Field, Alternating Gradient) cyclotrons, a concept invented in the fifties, will be shortly brought up.

16

The radiochemistry cyclotron in University of Helsinki

Helariutta K., Hakanen M., Solin O.

Nukleonika

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2003

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Vol. 48,suppl.2

173-174

EN

The 10 MeV proton cyclotron in the Laboratory of Radiochemistry, University of Helsinki is presented. Recent activities as well as the future research and teaching directions around the cyclotron are discussed.

17

The IBA self-extracting cyclotron project

Kleeven W., Lucas S., Delvaux J., Swoboda F., Zaremba S., Beeckman W., Vandeplassche D., Abs M.

Nukleonika

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2003

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Vol. 48,suppl.2

59-67

EN

The self-extracting cyclotron is a high-intensity 14 MeV H+ machine for isotope production. There is no electrostatic deflector. Extraction is achieved with a special shaping of the magnetic field. There are two long poles and two short poles, both with an elliptical gap profile; this provides a steep fall off of the magnetic field at the pole radii. An extraction groove is machined in the iron of one of the longer poles. First harmonic coils create a large orbit separation at the entrance of the extraction path and extract the beam. The machine is presently installed in the industrial isotope production site where the final commissioning and tests took place. Beams of more than 1.5 mA have been extracted and transported. Further development is ongoing in order to increase the current on target to at least 2 mA in the coming months. Commercial isotope production will start in the course of this year. The concept of the machine is explained and the layout of the machine and beam lines is presented. Results of orbit calculations and central region optimizations are given. Results of the measurement of extracted beam shapes and emittances are given. The progress and present status of the project are discussed.

18

Status report of the PSI high power proton cyclotrons

Humbel M., Adam S., Mezger A.

Nukleonika

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2003

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Vol. 48,suppl.2

141-144

EN

In addition to its traditional activities, of improving the availability of its 1 megawatt proton beam, the PSI cyclotron department has started two new projects. One of these is a further increase of the accelerated beam intensity towards 3 mA, the other one is a substantial enhancement of the proton therapy facility.

19

Status report of the LNS Superconducting Cyclotron

Rifuggiato D., Calabretta L., Cuttone G.

Nukleonika

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2003

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Vol. 48,suppl.2

131-134

EN

The LNS Superconducting Cyclotron has been working in stand alone mode since the beginning of 2000, after 5 years of operation as a booster of the 15 MV Tandem. The new mode has proven to be by far more advantageous than the previous one from the point of view of operation. Working with axial injection, a quite high number of new beam types has been developed. The new mode allows for acceleration of H2 + molecules, which break into two protons when crossing a stripper in the beam line out of the cyclotron. 62 MeV protons have been used for radiotherapy since February 2002. The new mode allows to inject a more intense beam as compared to the previous mode. Therefore, an upgrading program of the cyclotron has started, aiming at having an intense extracted beam to be used as a primary beam in a facility for production of radioactive beams. Beam tests have been accomplished to evaluate transmission figures, while the upgrading of the present electrostatic deflectors has started: new deflector systems, able to dissipate high beam power and allowing for easier maintenance, have been designed and will soon be tested in the machine.

20

Space charge dominated beam transport in the K130 cyclotron injection line

Heikkinen P.

Nukleonika

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2003

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Vol. 48,suppl.2

21-24

EN

High intensity H- beams are injected into the K130 cyclotron [1] for isotope production and for proton induced fission studies. Earlier, when protons were accelerated as positive ions, the beam intensity was limited by beam losses in the extraction system from the cyclotron. Stripping extraction of negative ions removed this limitation. However, now space charge effects in the injection beam line limit the beam intensity. At present, the maximum practical H- beam intensity at the inflector is about 0.25 mA, which gives 40-50 žA of extracted proton beam. Calculations predict that the injection beam line from the ion source to the matching quadrupoles below the cyclotron can transfer about 1 mA of 6 keV H- beam, which also was measured. The quadrupole section has a smaller transmission. Also a significant portion of the beam is lost during the last 2 m in the axial hole. General rules for maximum beam intensity as a function of beam line parameters such as beam tube aperture, distance of focusing elements, beam charge, mass and energy are given for different kinds of focusing systems (solenoids, FODO and FOFDOD quadrupole structures). As a conclusion, some suggestions to improve the transmission of the injection line are given.