Heteronuclear Gd-^99mTc 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(<b>1</b>)]} {<b>1</b> = DTPA-bis­(histidyl-amide); <i>M</i> = Re (<b>3a</b>); ^99mTc (<b>3b</b>)} 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 ^99mTc in the pair of histidylamide side arms. The two complexes are chemically equivalent as revealed by HPLC, and their “cocktail mixture” (<b>3a</b> + <b>3b</b>) 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

Gd Complexes of DO3A-(Biphenyl-2,2′-bisamides) Conjugates as MRI Blood-Pool Contrast Agents

We report the synthesis of DO3A derivatives of 2,2′-diaminobiphenyl (<b>1a</b>,<b>b</b>) and their Gd complexes of the type [Gd­(<b>1</b>)­(H₂O)]·<i>x</i>H₂O (<b>2a</b>,<b>b</b>) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of <b>2</b> compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The <i>R</i>₁ relaxivity in water reaches 7.3 mM^–1 s^–1, which is approximately twice as high as that of Dotarem (<i>R</i>₁ = 3.9 mM^–1 s^–1). They show interaction with HSA to give association constants (<i>K</i>_a) in the order of two (∼10²), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with <b>2</b> are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels. Furthermore, the brain tumor is vividly enhanced for an extended period of time

Gadolinium Complex of ¹²⁵I/¹²⁷I‑RGD-DOTA Conjugate as a Tumor-Targeting SPECT/MR Bimodal Imaging Probe

The work describes the synthesis and in vivo application of [Gd­(L)­(H₂O)]·<i>x</i>H₂O, where L is a (¹²⁵I/¹²⁷I-RGD)- DOTA conjugate, as a tumor-targeting SPECT/MR bimodal imaging probe. Here, (¹²⁵I/¹²⁷I-RGD)-DOTA signifies a “cocktail mixture” of radioisotopic (<b>1a</b>, L = ¹²⁵I-RGD-DOTA) and natural (<b>1b</b>, L = ¹²⁷I-RGD-DOTA) Gd complexes. The two complexes are chemically equivalent as revealed by HPLC, and their cocktail mixture exhibits the integrin-specific tumor enhancement, demonstrating that they constitute essentially a single bimodal imaging probe. Employment of a cocktail mixture thus proves to be a sole and practical approach to overcome the sensitivity difference problem between MRI and SPECT

Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (⁶⁸Ga/⁶⁴Cu) and therapy (¹⁷⁷Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which ¹⁷⁷Lu-L1 exhibited markedly higher uptake in HeLa cells than the ¹⁷⁷Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of ⁶⁸Ga-L1 and ⁶⁴Cu-L1 was clearly visualized in the tumor site, while ¹⁷⁷Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when ⁶⁸Ga-L1 or ⁶⁴Cu-L1 is used for diagnosis, ¹⁷⁷Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other

Manganese Complex of Ethylene­diamine­tetraacetic Acid (EDTA)–Benzothiazole Aniline (BTA) Conjugate as a Potential Liver-Targeting MRI Contrast Agent

A novel manganese­(II) complex based on an ethylene­diamine­tetraacetic acid (EDTA) coordination cage bearing a benzothiazole aniline (BTA) moiety (Mn-EDTA-BTA) was designed and synthesized for use as a liver-specific MRI contrast agent with high chelation stability. In addition to forming a hydrophilic, stable complex with Mn²⁺, this new Mn chelate was rapidly taken up by liver hepatocytes and excreted by the kidneys and biliary system. The kinetic inertness and <i>R</i>₁ relaxivity of the complex were much higher than those of mangafodipir trisodium (MnDPDP), a clinically approved liver-specific MRI contrast agent. The diagnostic utility of this new Mn complex in MRI was demonstrated by high-sensitivity tumor detection in an animal model of liver cancer

Gadolinium Complex of 1,4,7,10-Tetraazacyclo­dodecane-1,4,7-trisacetic Acid (DO3A)–Ethoxybenzyl (EOB) Conjugate as a New Macrocyclic Hepatobiliary MRI Contrast Agent

We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclo­dodecane-1,4,7-trisacetic acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a <i>T</i>₁ hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high <i>r</i>₁ relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging