High-performance liquid chromatographic (HPLC) analysis has shown that 99mTc-diphosphonate skeletal imaging agents are not pure chemical species, but rather are complicated mixtures of technetium-diphosphonate complexes. The focus of this project is the determination of exactly which isolated metal-diphosphonate complexes are the most effective agents for both diagnostic and therapeutic nuclear medicine applications. This will be accomplished through research bridging the disciplines of inorganic chemistry, analytical chemistry, radiology, nuclear medicine, and medicine. Preparative conditions used to generate metal-diphosphonate imaging agents will be varied in order to favor the production of specific metal-diphosphonate complexes, and then HPLC will be used to isolate these component complexes. These HPLC isolated components will be evaluated in animal models for (a) uptake on normal bone relative to uptake in soft tissues, and (b) uptake on abnormal bone (trauma-induced osteogenesis model) relative to uptake on normal bone. Those isolated metal-diphosphonate complexes containing 99m-Tc or 186-RE which appear most effective in animal models will be evaluated as diagnostic agents in human patients with established metastatic disease to bone. """"""""Instant kit"""""""" formulations will be developed in which the yields of the optimum 99mTc-diphosphonate diagnostic agents are maximized. The total therapeutic dose that could be delivered to a metastatic bone cancer site by an isolated metal-diphosphonate complex containing 186-Re, 32-P or 33-P will be estimated by external, conjugate view, counting of patients who have received diagnostic doses of isolated components, and by thermoluminescent dosimetry in animal models. Those components with appropriate scintigraphic and dosimetric properties will be evaluated as palliative therapeutic agents in human patients suffering from metastatic disease to the bone that is not-responsive to conventional therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032863-10
Application #
3170731
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1980-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Maxon 3rd, H R; Schroder, L E; Washburn, L C et al. (1998) Rhenium-188(Sn)HEDP for treatment of osseous metastases. J Nucl Med 39:659-63
Samaratunga, R C; Thomas, S R; Hinnefeld, J D et al. (1995) A Monte Carlo simulation model for radiation dose to metastatic skeletal tumor from rhenium-186(Sn)-HEDP. J Nucl Med 36:336-50
Englaro, E E; Schroder, L E; Thomas, S R et al. (1992) Safety and efficacy of repeated sequential administrations of Re-186(Sn)HEDP as palliative therapy for painful skeletal metastases. Initial case reports of two patients. Clin Nucl Med 17:41-4
Maxon 3rd, H R; Thomas, S R; Hertzberg, V S et al. (1992) Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases. Semin Nucl Med 22:33-40
Maxon 3rd, H R; Schroder, L E; Hertzberg, V S et al. (1991) Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo. J Nucl Med 32:1877-81
Maxon 3rd, H R; Schroder, L E; Thomas, S R et al. (1990) Re-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology 176:155-9
Holland, M E; Heineman, W R; Deutsch, E (1989) Technetium-99m complexes of dimethylaminomethylene diphosphonate (DMAD)--I. Anion exchange HPLC characterization of 99mTc(NaBH4)-DMAD mixtures. Int J Rad Appl Instrum B 16:301-11
Holland, M E; Bugaj, J; Heineman, W R et al. (1989) Technetium-99m complexes of dimethylaminomethylene diphosphonate (DMAD)--II. Biological distributions of 99mTc-DMAD components isolated by anion exchange HPLC. Int J Rad Appl Instrum B 16:313-7
Abdelnasser, M A; Deutsch, E; Heineman, W R (1989) Anion-exchange high-performance liquid chromatography of technetium-labeled phosphonoacetic acid skeletal imaging agent preparations. J Chromatogr 488:463-9
Maxon, H R; Deutsch, E A; Thomas, S R et al. (1988) Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies. Radiology 166:501-7

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