Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors.

Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors. Abstract Text:

Cristina ,P August Schubiger,Roger Schibli,

(99m)Tc-technetium ((99m)Tc) and (188)Re-rhenium ((188)Re) represent an interesting pair of radionuclides for diagnosis and therapy. The aim of this study was to synthesize and characterize in vitro/in vivo the first (188)Re-folate derivative [(188)Re(CO)(3)-picolylamine monoacetic acid 188/Re-OANA-folate (2)] for potential targeted radionuclide therapy of FR-positive tumors. The data were compared with those of the isostructural (99m)Tc-analog [(99m)Tc-PAMA folate (1)] reported previously. METHODS: In vitro stability of compound 2 was tested in phosphate-buffered saline and human plasma. Cell binding experiments were performed with FR-positive human KB cells. Biodistribution was assessed in female nude mice, bearing KB tumor xenografts. RESULTS: Cell binding experiments showed high and FR-specific uptake. In vivo, compound 2 accumulated specifically in the FR-positive tumors with maximal values 4 h post injection (p.i.) ['2: 1.87+/-0.04 percent injected dose per gram of weight tissue (% ID/g) vs. '1: 2.33+/-0.36% ID/g]. Unfavorably high retention of radioactivity was found in FR-positive kidneys (12.04+/-0.62% ID/g; 4 h p.i.). Tumor-to-blood ratio of radioactivity ('2: 14.5+/-1.32, 4 h p.i.) was lower than for compound '1 (58.0+/-12.2, 4 h p.i.), whereas tumor-to-kidney ratios were in the same range ('2: 0.15+/-0.01 vs. '1: 0.13+/-0.02, 4 h p.i.). Preadministration of the antifolate pemetrexed significantly improved the tumor-to-kidney ratio (2: 1.59+/-0.30, 4 h p.i.). CONCLUSIONS: The isostructural radiofolates 1 and '2 displayed almost identical pharmacokinetic profiles and accumulated both specifically in FR-positive tumors. However, only the coapplication of the antifolate pemetrexed improved the biodistribution of the radiotracers in such ways that a potential therapeutic application of compound '2 can be envisaged in the future.

Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors. Publishing Authors By Initials

C ,PA Schubiger,R Schibli,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research

PUBMED ID PMID:

MEDLINE DATE:

Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nuclear medicine and biology

VOLUME: 34

Page Numbers: 595-601

Journal Abbreviation: Nucl. Med. Biol.

ISSN: 0969-8051

DAY: 21

MONTH: Aug

YEAR: 2007

Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9304420

Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors. Keywords Mesh Terms:

KEYWORDS: Tissue Distribution

MESH TERMS: chemistry

Chemical & Substance for Abstract: Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors. Information

Substance Name: Technetium

Registry Number: 7440-26-8

Grant and Affiliation Information for Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors.

AFFILIATION: Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland.

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Nucl Med Biol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors Related Publications

• "Click-to-Chelate": Design and Incorporation of Triazole-Containing Metal-Chelating Systems into Biomolecules of Diagnostic and Therapeutic Interest.
• "Click-to-chelate": in vitro and in vivo comparison of a 99mTc(CO)3-labeled N(tau)-histidine folate derivative with its isostructural, clicked 1,2,3-triazole analogue.
• Cu(I)-catalyzed intramolecular cyclization of alkynoic acids in aqueous media: a "click side reaction".
• Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors.
• Production and separation of ''non-standard'' PET nuclides at a large cyclotron facility: the experiences at the Paul Scherrer Institute in Switzerland.
• [Finger Food. Eating independently with pleasure again]