Preparation of Radiolabeled Antibodies for Nuclear Medicine Applications in Immuno-Oncology

2021 ◽  
pp. 829-839
Author(s):  
Junnian Wei ◽  
David Y. Oh ◽  
Michael J. Evans
Keyword(s):  
Nuclear Medicine ◽  
Radiolabeled Antibodies

scholarly journals Automated Light-Induced Synthesis of 89Zr-Radiolabeled Antibodies for Immuno-Positron Emission Tomography

2021 ◽  
Author(s):  
Simon Klingler ◽  
Jason Holland
Keyword(s):  
Positron Emission Tomography ◽  
Nuclear Medicine ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Desferrioxamine B ◽  
Automated Method ◽  
Isolation And Characterization ◽  
Positron Emission ◽  
The Many ◽  
Radiolabeled Antibodies

Abstract Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography (PET) imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in <25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our Good Laboratory Practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in <25 min with an overall decay-corrected radiochemical yield of 20.1±2.4% (n=3), a radiochemical purity >99%, and chemical purity >99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

scholarly journals Automated light-induced synthesis of 89Zr-radiolabeled antibodies for immuno-positron emission tomography

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Simon Klingler ◽  
Jason P. Holland
Keyword(s):  
Positron Emission Tomography ◽  
Nuclear Medicine ◽  
Positron Emission Tomography Imaging ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Desferrioxamine B ◽  
Automated Method ◽  
Isolation And Characterization ◽  
Positron Emission ◽  
Radiolabeled Antibodies

AbstractClinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

Maximum image restoration in nuclear medicine

1990 ◽  
Vol 137 (3) ◽  
pp. 163 ◽  
Author(s):  
V.A. Oliveira ◽  
J.M. Nightingale
Keyword(s):  
Nuclear Medicine ◽  
Image Restoration

Impact of COVID-19 on Nuclear Medicine in Germany, Austria and Switzerland: An International Survey in April 2020

2020 ◽  
Vol 59 (04) ◽  
pp. 294-299 ◽  
Author(s):  
Lutz S. Freudenberg ◽  
Ulf Dittmer ◽  
Ken Herrmann
Keyword(s):  
Nuclear Medicine ◽  
Health Systems ◽  
Personal Protective Equipment ◽  
Large Scale ◽  
Diagnostic Procedures ◽  
Protective Equipment ◽  
Current Crisis ◽  
Web Based ◽  
Public Versus Private ◽  
The Impact

Abstract Introduction Preparations of health systems to accommodate large number of severely ill COVID-19 patients in March/April 2020 has a significant impact on nuclear medicine departments. Materials and Methods A web-based questionnaire was designed to differentiate the impact of the pandemic on inpatient and outpatient nuclear medicine operations and on public versus private health systems, respectively. Questions were addressing the following issues: impact on nuclear medicine diagnostics and therapy, use of recommendations, personal protective equipment, and organizational adaptations. The survey was available for 6 days and closed on April 20, 2020. Results 113 complete responses were recorded. Nearly all participants (97 %) report a decline of nuclear medicine diagnostic procedures. The mean reduction in the last three weeks for PET/CT, scintigraphies of bone, myocardium, lung thyroid, sentinel lymph-node are –14.4 %, –47.2 %, –47.5 %, –40.7 %, –58.4 %, and –25.2 % respectively. Furthermore, 76 % of the participants report a reduction in therapies especially for benign thyroid disease (-41.8 %) and radiosynoviorthesis (–53.8 %) while tumor therapies remained mainly stable. 48 % of the participants report a shortage of personal protective equipment. Conclusions Nuclear medicine services are notably reduced 3 weeks after the SARS-CoV-2 pandemic reached Germany, Austria and Switzerland on a large scale. We must be aware that the current crisis will also have a significant economic impact on the healthcare system. As the survey cannot adapt to daily dynamic changes in priorities, it serves as a first snapshot requiring follow-up studies and comparisons with other countries and regions.

Time-Dependent Characteristics of Sn-Complexes for Preparing 99mTc-Labelled Radiopharmaceuticals and their Bioavailabilities - a Review

1978 ◽  
Vol 17 (03) ◽  
pp. 110-125 ◽  
Author(s):  
O.P.D Noronha
Keyword(s):  
Nuclear Medicine ◽  
Time Dependent ◽  
Factors Affecting ◽  
99Mtc Radiopharmaceuticals

A review is made of some of the factors affecting bioavailability of diagnostic 99mTc-radiopharmaceuticals currently used in the practice of nuclear medicine.

Myocardial perfusion scintigraphy in Germany

2007 ◽  
Vol 46 (02) ◽  
pp. 49-55 ◽  
Author(s):  
W. Burchert ◽  
F. M. Bengel ◽  
R. Zimmermann ◽  
J. vom Dahl ◽  
W. Schäfer ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Myocardial Perfusion ◽  
Attenuation Correction ◽  
Working Group ◽  
Primary Care Physicians ◽  
Gated Spect ◽  
Myocardial Perfusion Scintigraphy ◽  
German Society ◽  
University Hospitals ◽  
Perfusion Scintigraphy

SummaryThe working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine (DGN), in cooperation with the working group Nuclear Cardiology of the German Cardiac Society (DGK), decided to conduct a national survey on myocardial perfusion scintigraphy (MPS). Method: A questionnaire to evaluate MPS for the year 2005 was sent. Results: 346 completed questionnaires had been returned (213 private practices, 99 hospitals and 33 university hospitals). MPS of 112 707 patients were reported with 110 747 stress and 95 878 rest studies. The majority (>75%) was performed with 99mTc-MIBI or tetrofosmin. 201Tl stress-redistribution was used in 22 637 patients (20%). The types of stress were exercise in 78%, vasodilation with adenosine or dipyridamol in 21% and dobutamine in 1%. 99.97% of all MPS were SPECT studies. Gated SPECT was performed in 36% of the stress and in 32% of the rest studies. An attenuation correction was used in 21%. 29 institutions (8%) performed gated SPECT (stress and rest) and attenuation correction. 47% of all MPS were requested by ambulatory care cardiologists, 17% by internists, 12% by primary care physicians, 21% by hospital departments and 2% by others. Conclusion: In Germany, MPS is predominantly performed with 99mTc-perfusion agents. The common type of stress is ergometry. Gated SPECT and attenuation correction do not yet represent standards of MPS practice in Germany, which indicates some potential of optimization.

Patient Exposure and Radiation Risk in Bulgarian Diagnostic Nuclear Medicine I. Survey of Diagnostic Nuclear Medicine Procedures in Bulgaria in 1980

1982 ◽  
Vol 21 (03) ◽  
pp. 85-91 ◽  
Author(s):  
R. Poppitz
Keyword(s):  
Nuclear Medicine ◽  
Radiation Risk ◽  
Patient Exposure ◽  
Diagnostic Nuclear Medicine ◽  
Nuklearmedizinische Diagnostik ◽  
Nuclear Medicine Procedures

Um die Strahlenexposition und das Strahlenrisiko für die Bevölkerung durch die nuklearmedizinische Diagnostik in Bulgarien zu ermitteln, wurde eine Erhebung für das Jahr 1980 über die Arten und Anzahl der Applikationen von Radiopharmaka, über die verwendeten Aktivitäten und über die Geschlechts- und Altersverteilung der untersuchten Patienten durchgeführt. Die Gesamtzahl diagnostischer in vivo Applikationen betrug 116418 (davon 40,5% bei Männern und 59,5% bei Frauen), d.h. 13,1 Applikationen per 1000 Einwohner. Die applizierte Gesamtaktivität aller 44 verwendeter Radiopharmaka betrug ca. 2,1 TBq (56 Ci). Die Geschlechts- und Altersverteilung der untersuchten Patienten war ähnlich jener in anderen Ländern: nur 17,4% aller Patienten waren im reproduktionsfähigen Alter, 52,7% waren über 45 Jahre alt. Im Vergleich zu anderen entwickelten Ländern war in Bulgarien im Jahr 1980 der Anteil der 131J-Jodid-Untersuchungen verhältnismäßig hoch.

Tc-99m Labeled Complexes of Aldehydes and Glutamate as Cholescintigraphic Agents

1975 ◽  
Vol 14 (04) ◽  
pp. 330-338
Author(s):  
L. G. Colombetti ◽  
J. S. Arnold ◽  
W. E. Barnes
Keyword(s):  
Nuclear Medicine ◽  
Gall Bladder ◽  
Rose Bengal ◽  
Valence State ◽  
Monosodium Glutamate ◽  
Kinetic Studies ◽  
Scintillation Camera ◽  
Blood Clearance ◽  
Lower Valence ◽  
Wire Basket

SummaryTc-99m pyridoxylidene glutamate has proven to be an excellent biliary scanning agent, far superior in many respect to the commonly used 1-131 rose bengal. The preparation of the compound as previously reported by Baker et al is too time consuming and requires the use of an autoclave which is not available in most nuclear medicine departments. In our facility, we have been preparing similar compounds using several aldehydes and monosodium glutamate to make labeled complexes having the same pharmacological characteristics. The mixture of monosodium glutamate, aldehyde, and Tc-99m pertechnetate is made slightly alkaline, purged with helium, and placed in a sealed vial. The vial, which is protected by a wire basket, is then heated in a laboratory oven at 130° C for a period of 15 to 20 minutes. During this time, the technetium is reduced to a lower valence state and bound to the complex formed. Chromatographic data show that these compounds are chemically similar to that previously reported. The compounds prepared concentrate in the gall bladder of the rabbit in less than 10 minutes. Kinetic studies have been performed on dogs with a scintillation camera and small digital computer to measure rates of blood clearance, liver and gall bladder uptake, and excretion into the intestine. The aldehyde — glutamate complex promises to be a useful scanning agent for the diagnosis of biliary and hepatocellular diseases.

A Simple Method for the Evaluation of Internal Doses in Nuclear Medicine

1974 ◽  
Vol 13 (02) ◽  
pp. 193-206
Author(s):  
L. Conte ◽  
L. Mombelli ◽  
A. Vanoli
Keyword(s):  
Nuclear Medicine ◽  
Close Agreement ◽  
Whole Body ◽  
Simple Method ◽  
Rapid Estimation ◽  
Absorbed Doses ◽  
The Mean ◽  
The Individual ◽  
Estimation Of Risk

SummaryWe have put forward a method to be used in the field of nuclear medicine, for calculating internally absorbed doses in patients. The simplicity and flexibility of this method allow one to make a rapid estimation of risk both to the individual and to the population. In order to calculate the absorbed doses we based our procedure on the concept of the mean absorbed fraction, taking into account anatomical and functional variability which is highly important in the calculation of internal doses in children. With this aim in mind we prepared tables which take into consideration anatomical differences and which permit the calculation of the mean absorbed doses in the whole body, in the organs accumulating radioactivity, in the gonads and in the marrow; all this for those radionuclides most widely used in nuclear medicine. By comparing our results with dose obtained from the use of M.I.R.D.'s method it can be seen that when the errors inherent in these types of calculation are taken into account, the results of both methods are in close agreement.

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