In vitro and in vivo characterization of novel water-soluble dithio-bisphosphine 99mTc complexes

Smith, Charles J.; Li, N.; Katti, Kattesh V.; Higginbotham, C.; Volkert, Wynn A.

doi:10.1016/s0969-8051(97)00100-5

Cited by 22 publications

(32 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The radiochemical characteristics (m vitro and in vivo behavior) of the corresponding tech-* Authors to whom correspondence should be addressed. netium-99m complex of this P 2 S 2 ligand has also been investigated [11]. These studies demonstrated the potential of tetradentate P 2 S 2 -ligand systems with hydroxymethyl-phosphine groups to produce, highly water-soluble, in vivo stable complexes.…”

Section: Introductionmentioning

confidence: 90%

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine ^99mTc Complex

Schibli¹,

Karra²,

Gali³

et al. 1998

Radiochimica Acta

Self Cite

View full text Add to dashboard Cite

The novel tetradentate, bifunctional chelating agent (BFCA) Dithia(bishydroxymethyl)bisphosphine (P 2 S 2 -COOH) was synthesized. The water-soluble ligand P 2 S 2 -COOH produces a Tc-99m-complex of radiochemical purity >95% at a BFCA concentration of 10~5 M by direct reduction of [TcO.,]" in presence of the ligand with Sn 2+ or by irans-chelation using "Tc-gluconate. HPLC analyses indicate the formation of a single species. The chromatographic retention time for this new technetium BFCA is similar to the correponding Re(V)-BFCA, suggesting the identical chemical structure on the tracer level. The "Tc-P 2 S 2 -COOH complex is stable over a wide range of pH (3-9) for >24 h. Biodistribution studies in the normal mouse model exhibited a fast clearance of the radioactivity from the bloodstream and excretion of the complex through the renal and the hepatobiliary pathways. The results of this investigations suggest that the phosphinethioether P 2 S 2 -chelate system is a possible alternative to the other bifunctional systems for the radiolabeling of site specific biomolecules with "Te and 186/188 R e .

show abstract

Section: Introductionmentioning

confidence: 90%

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine ^99mTc Complex

Schibli¹,

Karra²,

Gali³

et al. 1998

Radiochimica Acta

Self Cite

View full text Add to dashboard Cite

show abstract

“…33,34 The complexes of Tc-99m with the new chelating framework demonstrate excellent in vitro and in vivo stability and desirable clearance and excretion properties (from the blood stream). 29,32,34,35 This study describes an effective approach for synthesizing P 2 S 2 conjugated peptides to produce products in which the two hydroxymethylene phosphine (HMP) groups are not oxidized by convenient routes (e.g., automated SPPS is exceptionally challenging). For example, the HMP groups are oxidized when P 2 S 2 conjugated peptides synthesized by SPPS are cleaved from the resin by TFA.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Labeling with ^99mTc/¹⁸⁸Re of Peptide Conjugates Containing a Dithia-bisphosphine Chelating Agent

Gali

Hoffman²,

Sieckman³

et al. 2001

Bioconjugate Chem.

View full text Add to dashboard Cite

Radiolabeling of small receptor-avid peptides at specific predetermined chelation sites with radioactive metals has been an effective approach for production of target-specific radiopharmaceuticals for diagnosis and therapy of diseases. Among various electron-donating groups found on chelator frameworks, phosphines are unique because they display versatile coordination chemistry with a wide range of transition metals. We have recently reported the utility of a dithia-bis(hydroxymethyl)phosphine-based (P2S2) bifunctional chelating agent (BFCA) containing air-stable primary phosphine groups to form 99mTc-labeled receptor-avid peptides by the preconjugation approach. Here we report a novel strategy for labeling small peptides with both 99mTc and 188Re using the P2S2-COOH (6,8-bis[3-(bis(hydroxymethyl)phosphanyl)propylsulfanyl]octanoic acid) BFCA by a postconjugation radiolabeling approach. The first step in this approach involves the coupling of the corresponding (PH2)2S2-COOH intermediate to the N-terminus of the peptide(s). Formylation of P-H bonds with aqueous formaldehyde in the presence of HCl in ethanol affords the corresponding (hydroxymethyl)phosphine-P2S2-peptide conjugates in the form of an oxidatively stable phosphonium salt. The P2S2-peptide conjugates are generated (where the PH2 groups are converted to P(CH2OH)2 groups) by treatment of the P2S2-peptide phosphonium salt(s) with 1 M sodium bicarbonate solution at pH 8.5. Complexation of BFCA conjugates with 99mTc is achieved by direct reduction with Sn(II) tartarate to yield the 99mTc-P2S2-peptide conjugate in near quantitative yields. Complexation of the BFCA conjugates with 188Re is achieved by transchelation with 188Re citrate in yields of >/=90%. In this study, (PH2)2S2-COOH BFCA was conjugated to model peptides. The glycineglycine ethyl ester (GlyGlyOEt)-(PH2)2S2-COOH BFCA conjugate was converted to the hydroxymethylene phosphine form and complexed with 99mTc to produce the 99mTcO2-P2S2-GlyGlyOEt conjugate 8 in RCPs of >/=95%. This singular 99mTc product is stable over 24 h in aqueous solution as confirmed by HPLC. Identical retention times of the 99mTcO2-P2S2-GlyGlyOEt complex and its cold rhenium analogue (ReO2-P2S2-GlyGlyOEt) on HPLC indicates similarity in structures at the macroscopic and the tracer levels. The utility of this postconjugation strategy was further demonstrated by synthesizing a P2S2-D-Lys6-LHRH conjugate and producing its corresponding 99mTc complex in RCPs of >/=88%. Finally, the P2S2-5-Ava-BBN[7-14]NH2 bombesin (BBN) analogue was synthesized, the PH2 groups converted to P(CH2OH)2 groups and subsequently labeled with 188Re to yield a 188Re-labeled bombesin analogue with a RCP of >/=90%. The biological integrity of this conjugate was demonstrated in both in vitro and in vivo. The results of this investigation demonstrate that the (PH2)2S2-COOH BFCA can be conveniently used as a precursor for labeling small receptor-avid peptides with diagnostic (99mTc) and therapeutic (188Re) radionuclides via the postconjugation approach in hig...

show abstract

“…The ease with which P-H bonds in primary phosphines can be converted to P-C bonds, as shown in Schemes 9 and 10, demonstrates the importance of primary phosphines in the design and development of novel organophosphorus compounds. In particular, functionalized hydroxymethyl phosphines have become ubiquitous in the development of watersoluble transition metal/organometallic compounds for potential applications in biphasic aqueous-organic catalysis and also in transition metal based pharmaceutical development [53][54][55][56][57][58][59][60][61][62]. Extensive investigations on the coordination chemistry of hydroxymethyl phosphines have demonstrated unique stereospecific and kinetic propensity of this class of water-soluble phosphines [53][54][55][56][57][58][59][60][61][62].…”

Section: Formylation Reactions Of Primary Phosphinesmentioning

confidence: 99%

“…Representative examples outlined in Fig. 4, depict bidentate and multidentate coordination modes and the unique kinetic propensity to stabilize various oxidation states of metal centers, such as Re(V), Rh(III), Pt(II) and Au(I), in aqueous media [53][54][55][56][57][58][59][60][61][62]. Therefore, the importance of functionalized primary phosphines in the development of multidentate water-soluble phosphines cannot be overemphasized.…”

Section: Formylation Reactions Of Primary Phosphinesmentioning

confidence: 99%

New Vistas in Chemistry and Applications of Primary Phosphines

Katti¹,

Pillarsetty²,

Kannan³

2003

New Aspects in Phosphorus Chemistry III

View full text Add to dashboard Cite

Primary phosphines (R-PH 2 ) are an important class of compounds in organophosphorus chemistry. Although discovered over a century ago, their chemistry and applications have gained prominence in recent years. This review discusses recent developments on synthesis, molecular structure, properties, and applications of primary phosphines. In particular, discussions on synthesis and properties emphasize recent results from our laboratory on the chemical architecture of amide, thioether, and carboxylate functionalized primary bisphosphines. The utility of bromo-and aminopropyl phosphines (X(CH 2 ) 3 PH 2 ; X=Br or NH 2 ) as building blocks to produce 'designer' primary phosphines that display exceptional oxidative stability is described. The review also discusses the utility of carboxylate functionalized primary phosphines for incorporation on to peptides and their potential applications in catalysis and biomedicine.

show abstract

In vitro and in vivo characterization of novel water-soluble dithio-bisphosphine 99mTc complexes

Cited by 22 publications

References 16 publications

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine ^99mTc Complex

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine ^99mTc Complex

Synthesis, Characterization, and Labeling with ^99mTc/¹⁸⁸Re of Peptide Conjugates Containing a Dithia-bisphosphine Chelating Agent

New Vistas in Chemistry and Applications of Primary Phosphines

Contact Info

Product

Resources

About

In vitro and in vivo characterization of novel water-soluble dithio-bisphosphine 99mTc complexes

Cited by 22 publications

References 16 publications

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine 99mTc Complex

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine 99mTc Complex

Synthesis, Characterization, and Labeling with 99mTc/188Re of Peptide Conjugates Containing a Dithia-bisphosphine Chelating Agent

New Vistas in Chemistry and Applications of Primary Phosphines

Contact Info

Product

Resources

About

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine ^99mTc Complex

In Vitro and In Vivo Characterization of a Novel Bifunctionalized Water-Soluble Dithia-Bisphosphine ^99mTc Complex

Synthesis, Characterization, and Labeling with ^99mTc/¹⁸⁸Re of Peptide Conjugates Containing a Dithia-bisphosphine Chelating Agent