2002 Fiscal Year Final Research Report Summary
A Study on Tumor Uptake Mechanism of Radiolabeled Porphyrin Derivative
| Project/Area Number |
13670906
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
SHUKE Noriyuki Asahikawa Medical College, Radiology, Lecturer, 医学部, 講師 (50261417)
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| Co-Investigator(Kenkyū-buntansha) |
ABURANO Tamio Asahikawa Medical College, Radiology, Professor, 医学部, 教授 (30019963)
OSAKI Yoshinobu Asahikawa Medical College, Internal Medicine I, Lecturer, 医学部, 講師 (30191935)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Porphyrin derivative / ATN-10 / P388 / Pharmacokinetics |
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| Research Abstract |
Blood activity of a Tc-99m labeled prophirin derivative (ATN-10) was investigated in vitro and in vivo. Six percent of total activity was associated with the blood cells. Remaining 94 percent was in the plasma. HPLC analysis showed 47, 6, 7, 7, 9, 24 percent of the plasma activity was in the peaks of DTPA, β lipoprotein and macroglobulin, haptoglobin, α 1lipoprotein and haptoglobin, IgG, albumin, respectively. Tumor affinity and maximum binding of ATN-10 were investigated by cell binding assay with P388 leukemic cell line. Association constant (Ka) was 6.2 x 10^2, which was the same magnitude as those with plasma proteins such as albumin and tansferrin. The maximum binding was 3.1 x 10^9 / cell. The binding of ATN-10 and P388 was blocked by adding plasma into the assay medium, indicating free ATN-10 could bind to P388. Pharmacokinetics of ATN-10 in human was investigated on 3 normal volunteers by dose escalation study (0.1 and 0.5 mg dose/kg body weight). ATN-10 distributed mainly in the liver, bone marrow, kidney, bladder and intestine on whole body scintigram. Blood and organ kinetics of ATN-10 was related to the dose administered, showing nonlinear kinetics. Plasma activity of ATN-10 was not in single peak but dispersed in several peaks of the plasma constituents on HPLC analysis. These results indicated that ATN-10 was bound to several plasma constituents and the plasma constituents-bound ATN-10 could not be bound to the tumor cells. Pharmacokinetics of ATN-10 in human showed nonlinear blood or organ kinetics, indicating saturable binding with not only plasma constituents but metabolic organs such as the liver.
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Research Products
(2 results)
