Heteronuclear Gd-(99m)Tc Complex of DTPA-Bis(histidylamide) Conjugate as a Bimodal MR/SPECT Imaging Probe.

The work describes the synthesis and in vivo application of heterotrimetallic complexes of the type {Gd(H2O)[(M(H2O)(CO)3)2(1)]} {1 = DTPA-bis(histidyl-amide); M = Re (3a); (99m)Tc (3b)} for dual modality MR/SPECT imaging. Here, the DTPA-bis(histidylamide) conjugate functions as a trinucleating chelate incorporating Gd in the DTPA core with Re or (99m)Tc in the pair of histidylamide side arms. The two complexes are chemically equivalent as revealed by HPLC, and their "cocktail mixture" (3a + 3b) has demonstrated itself to be essentially a single bimodal imaging probe. The present system has thus overcome the sensitivity difference problem between MRI and SPECT and paved the way for practical applications.

[1]  Yongmin Chang,et al.  Gd complexes of macrocyclic diethylenetriaminepentaacetic acid (DTPA) biphenyl-2,2'-bisamides as strong blood-pool magnetic resonance imaging contrast agents. , 2011, Journal of medicinal chemistry.

[2]  Yongmin Chang,et al.  Gd-complexes of 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-1,4,7,10-tetraacetic acid (DOTA) conjugates of tranexamates as a new class of blood-pool magnetic resonance imaging contrast agents. , 2011, Journal of medicinal chemistry.

[3]  Jae-Chang Jung,et al.  Gold nanoparticles coated with gadolinium-DTPA-bisamide conjugate of penicillamine (Au@GdL) as a T1-weighted blood pool contrast agent , 2010 .

[4]  Ambika Bumb,et al.  Macromolecules, dendrimers, and nanomaterials in magnetic resonance imaging: the interplay between size, function, and pharmacokinetics. , 2010, Chemical reviews.

[5]  Angelique Louie,et al.  Multimodality imaging probes: design and challenges. , 2010, Chemical reviews.

[6]  J. Zubieta,et al.  Technetium and gallium derived radiopharmaceuticals: comparing and contrasting the chemistry of two important radiometals for the molecular imaging era. , 2010, Chemical reviews.

[7]  S. Caruthers,et al.  High Sensitivity: High-Resolution SPECT-CT/MR Molecular Imaging of Angiogenesis in the Vx2 Model , 2009, Investigative radiology.

[8]  Jinwoo Cheon,et al.  A hybrid nanoparticle probe for dual-modality positron emission tomography and magnetic resonance imaging. , 2008, Angewandte Chemie.

[9]  R. Kauppinen,et al.  Synthesis and spectroscopic properties of a prototype single molecule dual imaging agent comprising a heterobimetallic rhenium-gadolinium complex. , 2008, Journal of the American Chemical Society.

[10]  L. Marzilli,et al.  Initial evaluation of new 99mTc(CO)3 renal imaging agents having carboxyl-rich thioether ligands and chemical characterization of ReCO3 analogues. , 2007, Nuclear medicine and biology.

[11]  J. Seppenwoolde,et al.  Lanthanide-loaded liposomes for multimodality imaging and therapy. , 2006, Cancer biotherapy & radiopharmaceuticals.

[12]  J. Zubieta,et al.  Isostructural Re and 99mTc complexes of biotin derivatives for fluorescence and radioimaging studies. , 2006, Bioconjugate chemistry.

[13]  R. Price,et al.  Targeted molecular imaging agents for cellular-scale bimodal imaging. , 2004, Bioconjugate chemistry.

[14]  B. Spingler,et al.  Conjugation of a novel histidine derivative to biomolecules and labelling with [99mTc(OH2)3(CO)3]+. , 2004, Organic & biomolecular chemistry.

[15]  H. Spies,et al.  Chemical and biological characterization of technetium(I) and Rhenium(I) tricarbonyl complexes with dithioether ligands serving as linkers for coupling the Tc(CO)(3) and Re(CO)(3) moieties to biologically active molecules. , 2000, Bioconjugate chemistry.

[16]  R. Schibli,et al.  Organometallic 99mTc-aquaion labels peptide to an unprecedented high specific activity. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  Roger Schibli,et al.  Basic aqueous chemistry of [M(OH2)3(CO)3]+ (M=Re, Tc) directed towards radiopharmaceutical application , 1999 .