Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM

Neal G. Haynes, Jeffrey L. Lacy, Nisha Nayak, Chris S. Martin, Dayang Dai, Carla J. Mathias, Mark Green

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The 62Zn62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4- methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. Methods: The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 μA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCI, 0.2 mol/L HCI) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 μm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. Results: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7 ± 0.2 GBq (46.7 ± 5.6 mCi), and yield was 72% ± 16%. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4% ± 2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8 ± 0.2 GBq (20.5 ± 5.3 mCi) with no adverse side effects. Conclusion: Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.

Original languageEnglish (US)
Pages (from-to)309-314
Number of pages6
JournalJournal of Nuclear Medicine
Volume41
Issue number2
StatePublished - Feb 2000
Externally publishedYes

Fingerprint

Cyclotrons
Radiopharmaceuticals
Syringes
Perfusion
Clinical Trials
Germanium
Pyruvaldehyde
Technetium Tc 99m Sestamibi
Costs and Cost Analysis
Myocardial Perfusion Imaging
United States Food and Drug Administration
Practice Guidelines
Endotoxins
Isotopes
Infertility
Half-Life
Protons
Copper
Coronary Artery Disease
Spectrum Analysis

Keywords

  • Zn/Cu generator
  • Myocardial perfusion
  • PET radiopharmaceuticals
  • Pyruvaldehyde-bis(n4- methylthiosemicarbazone)

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Haynes, N. G., Lacy, J. L., Nayak, N., Martin, C. S., Dai, D., Mathias, C. J., & Green, M. (2000). Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM. Journal of Nuclear Medicine, 41(2), 309-314.

Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM. / Haynes, Neal G.; Lacy, Jeffrey L.; Nayak, Nisha; Martin, Chris S.; Dai, Dayang; Mathias, Carla J.; Green, Mark.

In: Journal of Nuclear Medicine, Vol. 41, No. 2, 02.2000, p. 309-314.

Research output: Contribution to journalArticle

Haynes, NG, Lacy, JL, Nayak, N, Martin, CS, Dai, D, Mathias, CJ & Green, M 2000, 'Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM', Journal of Nuclear Medicine, vol. 41, no. 2, pp. 309-314.
Haynes NG, Lacy JL, Nayak N, Martin CS, Dai D, Mathias CJ et al. Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM. Journal of Nuclear Medicine. 2000 Feb;41(2):309-314.
Haynes, Neal G. ; Lacy, Jeffrey L. ; Nayak, Nisha ; Martin, Chris S. ; Dai, Dayang ; Mathias, Carla J. ; Green, Mark. / Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM. In: Journal of Nuclear Medicine. 2000 ; Vol. 41, No. 2. pp. 309-314.
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abstract = "The 62Zn62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4- methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. Methods: The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 μA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCI, 0.2 mol/L HCI) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2{\%} EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 μm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. Results: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7 ± 0.2 GBq (46.7 ± 5.6 mCi), and yield was 72{\%} ± 16{\%}. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4{\%} ± 2.4{\%}. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8 ± 0.2 GBq (20.5 ± 5.3 mCi) with no adverse side effects. Conclusion: Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.",
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author = "Haynes, {Neal G.} and Lacy, {Jeffrey L.} and Nisha Nayak and Martin, {Chris S.} and Dayang Dai and Mathias, {Carla J.} and Mark Green",
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TY - JOUR

T1 - Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM

AU - Haynes, Neal G.

AU - Lacy, Jeffrey L.

AU - Nayak, Nisha

AU - Martin, Chris S.

AU - Dai, Dayang

AU - Mathias, Carla J.

AU - Green, Mark

PY - 2000/2

Y1 - 2000/2

N2 - The 62Zn62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4- methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. Methods: The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 μA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCI, 0.2 mol/L HCI) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 μm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. Results: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7 ± 0.2 GBq (46.7 ± 5.6 mCi), and yield was 72% ± 16%. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4% ± 2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8 ± 0.2 GBq (20.5 ± 5.3 mCi) with no adverse side effects. Conclusion: Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.

AB - The 62Zn62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4- methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. Methods: The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 μA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCI, 0.2 mol/L HCI) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 μm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. Results: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7 ± 0.2 GBq (46.7 ± 5.6 mCi), and yield was 72% ± 16%. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4% ± 2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8 ± 0.2 GBq (20.5 ± 5.3 mCi) with no adverse side effects. Conclusion: Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.

KW - Zn/Cu generator

KW - Myocardial perfusion

KW - PET radiopharmaceuticals

KW - Pyruvaldehyde-bis(n4- methylthiosemicarbazone)

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