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

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

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

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

Preliminary PET Study of ¹⁸F‑FC119S in Normal and Alzheimer’s Disease Models

To evaluate the efficacy of ¹⁸F-FC119S as a positron emission tomography (PET) radiopharmaceutical for the imaging of Alzheimer’s disease (AD), we studied the drug absorption characteristics and distribution of ¹⁸F-FC119S in normal mice. In addition, we evaluated the specificity of ¹⁸F-FC119S for β-amyloid (Aβ) in the AD group of an APP/PS1 mouse model and compared it with that in the wild-type (WT) group. The behavior of ¹⁸F-FC119S in the normal mice was characteristic of rapid brain uptake and washout patterns. In most organs, including the brain, ¹⁸F-FC119S reached its maximum concentration within 1 min and was excreted via the intestine. Brain PET imaging of ¹⁸F-FC119S showed highly specific binding of the molecule to Aβ in the cortex and hippocampus. The brain uptake and binding values for the AD group were higher than those for the WT group. These results indicated that ¹⁸F-FC119S would be a candidate PET imaging agent for targeting Aβ plaque