Accession Number DE2012-1034900
Title Preparation of Radiopharmaceuticals Labeled with Metal Radionuclides, (Final Report).
Publication Date Feb 2012
Media Count 7p
Personal Author M. J. Welch
Abstract The overall goal of this project was to develop methods for the production of metal-based radionuclides, to develop metal-based radiopharmaceuticals and in a limited number of cases, to translate these agents to the clinical situation. Initial work concentrated on theapplication of the radionuclides of Cu, Cu-60, Cu-61 and Cu-64, as well as application of Ga-68 radiopharmaceuticals. Initially Cu-64 was produced at the Missouri University Research Reactor and experiments carried out at Washington University. A limited number of studies were carried out utilizing Cu-62, a generator produced radionuclide produced by Mallinckrodt Inc. (now Covidien). In these studies, copper-62-labeledpyruvaldehyde Bis(N(sup 4)-methylthiosemicarb azonato)-copper(II) was studied as an agent for cerebral myocardial perfusion. A remote system for the production of this radiopharmaceutical was developed and a limited number of patient studies carried out with this agent. Various other copper radiopharmaceuticals were investigated, these included copper labeled blood imaging agents as well as Cu-64 labeled antibodies.Cu-64 labeled antibodies targeting colon cancer were translated to the human situation. Cu-64 was also used to label peptides (Cu-64 octriatide) and this is one of the first applications of a peptide radiolabeled with a positron emitting metal radionuclide. Investigationswere then pursued on the preparation of the copper radionuclides on a small biomedical cyclotron. A system for the production of high specificactivity Cu-64 was developed and initially the Cu-64 was utilized to study the hypoxic imaging agent Cu-64 ATSM. Utilizing the same target system, other positron emitting metal radionuclides were produced, thesewere Y-86 and Ga-66. Radiopharmaceuticals were labeled utilizing both ofthese radionuclides. Many studies were carried out in animal models on the uptake of Cu-ATSM in hypoxic tissue. The hypothesis is that Cu-ATSM retention in vivo is dependent upon the oxygen retention of the tissue and the significantly greater retention amounting in hypoxic tissue. This hypothesis was confirmed in a series of animal studies. Cu-64 can be used both as an imaging radionuclide and a therapeutic radionuclide. The therapeutic efficacy of Cu-64 ATSM was proven in hamsters bearing the CW39 human colorectal tumors. The administration of Cu-64 ATSM significantly increased the survival time of tumor-bearing animals with no acute toxicity. This copper agent therefore shows promise for radiotherapy. The flow tracer Cu-64 PTSM also demonstrates therapeutic potential by inhibiting cancer cells implanted in animal models. Again, this inhibition occurred at doses which showed no sign of toxicity to the animals. Cu-ATSM was translated to humans, under other support a series of tumors were investigated; these included head and neck cancer,non-small cell lung cancer, cervical cancer and renal cancer. Another radionuclide that was investigated was titanium 45. This radionuclide was successfully produced by radiation of a scandium foil with 15 MeV protons.
Keywords Copper
Dimers
In vitro
In vivo
Nuclear medicine
Positrons
Radiology
Radiopharmaceuticals
Survival time
Titanuim


 
Source Agency Technical Information Center Oak Ridge Tennessee
NTIS Subject Category 57V - Radiobiology
99F - Physical & Theoretical Chemistry
Corporate Author Washington Univ., St. Louis, MO.
Document Type Technical report
Title Note N/A
NTIS Issue Number 1221
Contract Number DE-FG02-87ER60512

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