Methods for compact cyclotron production of indium-111 for medical use

Abstract Purpose We demonstrate cyclotron production of high-quality 225Ac using an electroplated 226Ra target. Methods 226Ra was extracted from legacy Ra sources using a chelating resin. Subsequent ion-exchange purification gave pure 226Ra with a certain amount of carrier Ba. The radium target was prepared by electroplating. We successfully deposited about 37 MBq of 226Ra on a target box. Maximum activation was achieved using 15.6 MeV protons on the target at 20 µA for 5 h. Two functional resins with various concentrations of nitric acid purified 225Ac and recovered 226Ra. Cooling the intermediate 225Ac for 2–3 weeks decayed the major byproduct of 226Ac and increased the radionuclidic purity of 225Ac. Repeating the same separation protocol provided high-quality 225Ac. Results We obtained 225Ac at a yield of about 2.4 MBq at the end of bombardment (EOB), and the subsequent initial purification gave 1.7 MBq of 225Ac with 226Ac/225Ac ratio of < 3% at 4 days from EOB. Additional cooling time coupled with the separation procedure (secondary purification) effectively increased the 225Ac (4n + 1 series) radionuclidic purity up to 99 + %. The recovered 225Ac had a similar identification to commercially available 225Ac originating from a 229Th/225Ac generator. Conclusion This procedure, which involves the 226Ra(p,2n)225Ac reaction and the appropriate purification, has the potential to be a major alternative pathway for 225Ac production because it can be performed in any facility with a compact cyclotron to address the increasing demand for 225Ac.

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Cyclotron Production of 225Ac from an electroplated 226Ra Target

10.21203/rs.3.rs-276600/v1 ◽

2021 ◽

Author(s):

Kotaro Nagatsu ◽

Hisashi Suzuki ◽

Masami Fukada ◽

Taku Ito ◽

Jun Ichinose ◽

...

Keyword(s):

Alternative Pathway ◽

Chelating Resin ◽

Separation Procedure ◽

Purification Procedure ◽

Radionuclidic Purity ◽

High Quality ◽

Cyclotron Production ◽

Compact Cyclotron ◽

Increasing Demand ◽

Mev Protons

Abstract Purpose We demonstrate a cyclotron production of high-quality 225Ac using an electroplated 226Ra target. Methods All 226Ra used in this work was extracted from legacy Ra sources using a chelating resin. The subsequent ion-exchange purification gave pure 226Ra with a certain amount of carrier Ba. The radium target was prepared by electroplating. We successfully deposited about 1 mg (mCi) of 226Ra on a target box. Activation was performed by 16.5 MeV protons (on the target) at 20 µA for 5 h as the maximum. Purification of 225Ac as well as 226Ra recovery was performed using two functional resins with various concentrations of nitric acid. Cooling of the intermediate 225Ac for 2–3 weeks decayed the major byproduct of 226Ac and increased the radionuclidic purity of 225Ac. Then the same separation protocol was repeated to provide high-quality 225Ac. Results We obtained 225Ac at a yield of about 2.4 MBq (65 µCi) at EOB, and the subsequent primal purification gave 1.7 MBq (48 µCi) of 225Ac with 226Ac/225Ac ratio of < 4% at 4 d from EOB. Additional cooling time coupled with the repeated separation procedure (secondary purification) effectively increased the 225Ac (4n + 1 series) radionuclidic purity up to 99+%, which showed a similar identification to a commercially available 225Ac originating from a 229Th/225Ac generator. Conclusion The 226Ra(p,2n)225Ac reaction and the appropriate purification procedure has the potential to be a major alternative pathway for 225Ac production and can be performed in any facility with a compact cyclotron to address the increasing demand for 225Ac.

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Cyclotron production of carrier-free indium-111

The International Journal of Applied Radiation and Isotopes ◽

10.1016/0020-708x(72)90002-6 ◽

1972 ◽

Vol 23 (2) ◽

pp. 57-58 ◽

Cited By ~ 35

Author(s):

L.C. Brown ◽

A.L. Beets

Keyword(s):

Cyclotron Production ◽

Carrier Free ◽

Indium 111

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Indium-111 labeling of low density lipoproteins (LDL) with the DTPA-bis(stearylamide) for tumor localization: first imaging and biodistribution in B16 tumored mice

Journal de Chimie Physique ◽

10.1051/jcp/1996930128 ◽

1996 ◽

Vol 93 ◽

pp. 128-131 ◽

Cited By ~ 4

Author(s):

F Jasanada ◽

P Urizzi ◽

JP Souchard ◽

G Favre ◽

A Boneu ◽

...

Keyword(s):

Low Density Lipoproteins ◽

Tumor Localization ◽

Low Density ◽

Indium 111

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Bone Marrow Scintigraphy in Patients Treated with Chemotherapy and/or Radiotherapy

Nuklearmedizin ◽

10.1055/s-0037-1620613 ◽

1977 ◽

Vol 16 (02) ◽

pp. 86-88

Author(s):

V. Foltýnová ◽

E. Vétrovcová ◽

E. Tichá ◽

J. Brousil

Keyword(s):

Bone Marrow ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Detailed Knowledge ◽

General State ◽

Bone Marrow Scintigraphy ◽

Indium 111

SummaryBone marrow scintigraphy after the application of indium 111 In was compared with the results of bone marrow puncture in 18 patients with Hodgkin's disease treated with radiotherapy and/or chemotherapy. Agreement was found in 85% of the cases. When the results of bone marrow puncture were compared with the general state of haemopoiesis estimated scintigraphically agreement was found in only 65%. Bone marrow scintigraphy gives a more detailed knowledge of the general state of haemopoiesis and serves as a guide for the control of therapy with cytostatics and/or irradiation.

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Preparation of a Viable Population of Indium-111- Labelled Human Blood Platelets

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657048 ◽

1979 ◽

Vol 42 (05) ◽

pp. 1473-1482 ◽

Cited By ~ 17

Author(s):

A Dup Heyns ◽

P N Badenhorst ◽

H Pieters ◽

M G Lötter ◽

P C Minnaar ◽

...

Keyword(s):

Platelet Rich Plasma ◽

Blood Platelets ◽

Kinetic Studies ◽

Physiological Saline ◽

Human Platelets ◽

Autologous Plasma ◽

Platelet Suspension ◽

Viable Population ◽

Indium 111

SummaryFactors influencing labelling of human platelets with 111Indium-8-hydroxyquinoline ([111In]-oxine) in a physiological saline medium were investigated. The efficiency of labelling is influenced by time of incubation, concentration of oxine, and pH of the incubating medium. It was found that a viable platelet population could be labelled under the following conditions: (1) centrifugation of platelet rich plasma in polystyrene conical tubes at 800 g for 15 min; (2) resuspension of the platelet pellet in saline, pH 5.5; (3) incubating for 30 min at 22°C with [111In]-oxine at a concentration of 6.25 mg oxine/litre platelet suspension; (4) washing once with platelet poor autologous plasma (PPP); and (5) finally resuspending the platelets in PPP. The labelled platelets aggregated normally with collagen and ADP. Electron microscopy, done immediately after labelling, showed internal organelle reorganization characteristic of activated platelets. These ultrastructural features were reversible on incubation in PPP at 37°C for 30 min. The 111In is not released from aggregated platelets and the label does not elute from incubated platelets for at least five hr. We conclude that human platelets thus labelled are suitable for in vivo kinetic studies.

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Urinary Beta-Thromboglobulin Correlates with Impairment of Renal Function in Patients with Diabetic Nephropathy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661646 ◽

1986 ◽

Vol 56 (02) ◽

pp. 229-231 ◽

Cited By ~ 2

Author(s):

A H Hopper ◽

H Tindall ◽

J A Davies

Keyword(s):

Renal Function ◽

Diabetic Nephropathy ◽

Microvascular Disease ◽

Normal Subjects ◽

Specific Protein ◽

Creatinine Concentration ◽

Β2 Microglobulin ◽

Plasma Creatinine Concentration ◽

Insulin Dependent ◽

Indium 111

SummaryTBeta-thromboglobulin (βTG) is a platelet-specific protein and since its concentration in plasma rises when platelets are activated, it has been used as an indicator of platelet involvement in vascular disease. Since platelets might be involved in the pathogenesis of diabetic microvascular disease we measured urinary βTG in 20 insulin-dependent diabetics with nephropathy and compared the results with those from 20 normal subjects. Measurement of βTG in urine was undertaken to avoid errors induced by blood sampling and to gain information over a prolonged period using a single assay. Measurements were made of βTG, β2-microglobulin and total protein in urine collected for 24 h and creatinine and β2 microglobulin in plasma. Survival of indium-111-labelled platelets was measured in nine patients. Urinary PTG was significantly (p <0.02) increased in the 20 patients compared with 20 normal volunteers (median value 1.3 vs 0.8 μg/24 h). There was a strong correlation between urinary βTG excretion and plasma creatinine concentration (r = 0.8, p <0.0001) and plasma β2-microglobulin concentration (r = 0.9, p <0.0001). Urinary βTG concentration did not correlate with platelet survival. The results indicate that although urinary βTG is significantly increased in patients with diabetic nephropathy its concentration in urine correlates with indicators of glomerular filtration rather than with a test of platelet activation.

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CITOTOXICITY OF INDIUM-111-LABELED AUTOLOGOUS WBC

Токсикологический вестник ◽

10.36946/0869-7922-2019-1-18-22 ◽

2019 ◽

pp. 18-22

Author(s):

K. A. Luneva ◽

K. E. Ternovskaya ◽

O. E. Klement’eva ◽

A. S. Lunev

Keyword(s):

Cytotoxic Effect ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Blood Leukocytes ◽

Cytotoxic Effects ◽

Indium 111 ◽

Single Photon Emission Computed ◽

Photon Emission Computed Tomography ◽

Subsequent Introduction

The radiopharmaceutical precursor «Oxind, 111In» is a complex compound for labeling autologous leukocytes of human blood and their subsequent introduction for non-specific visualization and localization of inflammation foci of different nature by single-photon emission computed tomography (SPECT). The cytotoxic effect of lyophilisate for preparation of radiopharmaceutical preparation «Oxind, 111In» and its radiopharmaceutical precursor on rabbit blood leukocytes has been investigated. In the course of studies of the cytotoxicity of the lyophilisate for the preparation of a radiopharmaceutical precursor with successively increasing concentrations of the main substance, 8-hydroxyquinoline, the permissible concentrations have been determined and the absolutely cytotoxic concentration was achieved.In the study of the cytotoxic effect of the precursor of radiopharmaceutical on two dosages that differ by 10 times in volume activities (MBq / ml), the absence of cytotoxic effects has been confirmed.

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