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Despite the seeming overall advantages of 62Cu radiopharmaceuticals in PET imaging, there also remains considerable interest in agents derived from 64Cu, in particular, the hypoxia agent 64Cu-ATSM. With its longer 12.7-hour half-life, 64Cu can easily be prepared by known targetry methods at cyclotron production centers and distributed to clinical sites by overnight express delivery across in the continental United States. An advantage of 64Cu over other copper radioisotopes is its lower positron emission energy, which results in decreased image blurring and better spatial resolution in PET imaging. The extended half-life allows PET images to be acquired over a much longer time period than with other Copper PET imaging agents.
Washington University, St Louis has utilized 60Cu-ATSM in PET imaging of approximately 100 patients having a variety of cancers, including non-small cell lung, head and neck, cervical, breast, brain, and rectal cancers. An IND was filed to utilize the more convenient 64Cu-ATSM agent in a study of advanced cervical cancer patients. Expansion of this IND to a multi-site clinical trial for the diagnosis and staging of cervical cancer is currently in progress. Previous studies at Washington University used a complicated onsite preparation and purification methodology for labeled 64Cu-ATSM, which is not readily amenable to multi-site clinical studies, since highly trained personnel and radiopharmacy facilities that are generally not available in the clinical setting are required.
Proportional Technologies, Inc. has developed a high capacity H2ATSM lyophilized kit specifically meeting the requirements of higher capacity needed for 64Cu-ATSM preparation. This kit provides instant synthesis at radiochemical purity > 95% simply by mixing ionic 64Cu and the reconstituted kit solution. No complicated purification is required and once prepared at the clinical site the solution remains stable for at least 4 hours.
Proportional Technologies, Inc. also provides a wide choice of BTS ligand kits for onsite instant labeling using 64Cu and other non-generator produced copper radionuclide’s such as 67Cu, 60Cu and 61Cu. These kits are easily adapted and utilized for various custom animal studies. The current available kits include:
ATSM04UG / REC02-10ML
Medium Capacity 4 µg H2ATSM kit for 64Cu and other Cu isotopes
Injectable Solution: pyrogen free isotonic solution
Cu Capacity*: 1.0 µg
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Suggested Application: clinical** & preclinical studies
User’s Manual for Labeling
ATSM400NG / REC02-5ML
Small Capacity 0.4 µg H2ATSM kit for 64Cu and other Cu isotopes
Injectable Solution: sterile and pyrogen free isotonic solution
Cu Capacity*: 0.1 µg
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Suggested Application: Clinical*** & preclinical studies
User’s Manual for Labeling
PTSM02UG / REC02-5ML
Small Capacity 2 µg H2PTSM kit for 64Cu and other Cu isotopes
Injectable Solution: sterile and pyrogen free isotonic solution
Cu Capacity*: 0.5 µg
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Suggested Application: Clinical*** & preclinical studies
User’s Manual for Labeling
ETS02UG / REC02-5ML
Small Capacity 2 µg H2ETS kit for 64Cu and other Cu isotopes
Injectable Solution: sterile and pyrogen free isotonic solution
Cu Capacity*: 0.5 µg
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Suggested Application: Clinical*** & preclinical studies
User’s Manual for Labeling
Buffer Solutions
Various sterile and pyrogen free buffer solutions with custom concentrations and extremely low metal content, adapted for use in various metal labeling processes.
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OASIS Q/A Kit
Package for convenient and quick assay of radiochemical purity for labeled compounds. Our investigation shows that Oasis results are as accurately as HPLC measurements for labeling yield >70%****.
Sold in packages of:
1 Oasis Q/A Measurement Kit $ 9.28
10 Oasis Q/A Measurement Kits $ 85.73
Requests:
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* Ligand capacity to accommodate cold copper in non-generator produced 64Cu solution. So far, almost all the 64Cu available in the market is “contaminated” with cold copper. Please read the following section of “Rationale for “High Capacity” ATSM kit” to be aware of this issue.
** Clinical studies will soon be available through DMF reference. Filtration required prior to injection.
*** Clinical studies available by DMF reference.
**** HPLC Validation and Q/A of 62Cu-PTSM, 62Cu-ATSM, and 62Cu-ETS Synthesized by 62Zn/62Cu Microgenerator Kit, SNM 2006 annual meeting.
Rationale for “High Capacity” ATSM kit
A special kit is required for 64Cubecause the specific activity of the commercially prepared 64Cu is much lower than that of generator produced 62Cu Because of the very short half life of 62Cu the intrinsic specific activity is an incredibly high to 300 Ci/µg. When 62Cu is produced by a generator it is possible to approach such high specific activity in the eluted product because the generator column does not retain any cold copper or other noncomplexing metals from the target purification process. That means that each time the generator is eluted any metal level arising from target metals decreases with successive elutions. Thus typically the PTI 62Cu specific activity exceeds 1000 mCi/µg of cold Cu facilitating use of exceedingly small capacity ligand kits. Commercial production of 64Cu uses the p,n reaction on enriched 64Ni that must be plated on a substrate metal. Any cold copper present in the 64Ni or that is etched from the target backing is impossible to separate from the 64Cu. Because the 64Ni is very expensive it must be reclaimed and used over and over in order to achieve economically acceptable production of 64Cu. Because of these factors the specific activity of commercial 64Cu ranges from 50 – 200 mCi/µg and is much lower than the intrinsic specific activity of 64Cu which is 3.8 Ci/µg (click here for a specific activity calculator).
When 64Cu is shipped overnight specific activity is lost at the rate at which 64Cu decays. So on the day following irradiation the specific activity degrades by 4 fold or more to ~ 10mCi/ug. The injected activity targeted in planned multicenter trials is 25 mCi. Accounting for the molecular weight difference of 63.5 versus 260.5 over 15 μg of H2ATSM is required to handle this level of copper with some excess capacity. To meet this need a high capacity 64Cu-ATSM kit containing 15 μg of ATSM ligand is under development. The GMP processing of this kit will soon be filed in a Drug Master File so that the kit can be utilized in investigational human studies. As a predecessor to this development PTI developed a smaller capacity 4 μg H2ATSM kit that is available for preclinical studies. In addition the 0.4 μg H2ATSM 62Cu kit can be supplied for small animal studies.
How to order
For more information, pricing, and to place an order, please call toll-free 800-759-7325, or email us at
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Downloads
Automation & Improved Performance of a 62Zn/62Cu Microgenerator System (download)
High Capacity High H2ATSM Kits for On-Site Synthesis of Hypoxia-Specific Agent 64Cu-ATSM (download)
HPLC Validation and Q/A of 62Cu-PTSM, 62Cu-ATSM, and 62Cu-ETS Synthesized by 62Zn/62Cu Microgenerator Kit (download)
QC Performance of a 62Zn→62Cu Microgenerator System for use in PET (download)
Funding
This technology has been funded by the NIH under the project name “Kits for Instant Synthesis of 64Cu-ATSM" – EB008945.
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