Blood Pool Effect Research Articles

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 (1a,b) and their Gd complexes of the type [Gd(1)(H2O)]·xH2O (2a,b) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The R 1 relaxivity in water reaches 7.3 mM(-1) s(-1), which is approximately twice as high as that of Dotarem (R 1 = 3.9 mM(-1) s(-1)). They show interaction with HSA to give association constants (K a) in the order of two (∼10(2)), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with 2 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.

Gd Complexes of Macrocyclic Diethylenetriaminepentaacetic Acid (DTPA) Biphenyl-2,2′-bisamides as Strong Blood-Pool Magnetic Resonance Imaging Contrast Agents

We report the synthesis of macrocyclic DTPA conjugates of 2,2'-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H(2)O)]·xH(2)O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R(1) relaxivity reaches 10.9 mM(-1) s(-1), which is approximately 3 times as high as that of structurally related Gd-DOTA (R(1) = 3.7 mM(-1) s(-1)). The R(1) relaxivity in HSA goes up to 37.2 mM(-1) s(-1), which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect.

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

Gd-complexes of the type [Gd(L)(H(2)O)]·xH(2)O (5a-c), where L is DOTA conjugates of tranexamic acid (4a) and tranexamic esters (4b,c), have been prepared as a new class of MRI blood-pool contrast agents (BPCAs). Thermodynamic stability (K(GdL)) and pharmacokinetic inertness of 5 compare well with or better than those of analogous MRI contrasting agents (CAs) such as Gd-DOTA and Gd-DTPA-BMA. Their R(1)-relaxivities are significantly higher than those of any of the clinically used MRI CAs. T(1)-weighted MR images of mice administered by 5c demonstrate high blood-pool effect with simultaneous contrast enhancement in liver. The structural uniqueness of 5c lies in the fact that it adopts macrocyclic DOTA instead of acyclic DTPA. In addition, 5c is nonionic and makes no resort to aromatic substituent(s) in the chelate backbone for the blood-pool enhancement. The nature of hepatobiliary uptake demonstrated by 5c may be explained in terms of lipophilicity of tranexamate in the chelate (4c). The cell cytotoxicity test shows no toxicity found with 5, suggesting their use as a practical MRI BPCAs.

Non-invasive imaging in the diagnosis of acute viral myocarditis

Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1–10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail.

Imaging Characteristics of DHOG, a Hepatobiliary Contrast Agent for Preclinical MicroCT in Mice

This study was performed to assess the imaging characteristics and pharmacokinetics of 1,3-Bis-[7-(3-amino-2,4,6-triiodophenyl)-heptanoyl]-2-oleoyl glycerol (DHOG, Fenestra LC), a hepatobiliary contrast agent for microCT. We investigated the abdomen of 18 female C3H mice in a MicroCAT II microCT scanner before contrast agent injection and at multiple time points up to 48 hours after intravenous injection of DHOG (1 g I/kg body weight). The contrast agent effect was determined quantitatively and dynamically by measuring pre- and postcontrast Hounsfield units (HU) of the liver, aorta, spleen, and kidneys. Based on additional phantom measurements, the reproducibility of lesion detection was estimated for different lesion sizes. DHOG caused a marked early postcontrast enhancement of blood in the aorta and a very high enhancement of the spleen, both slowly declined after 90 minutes. The liver parenchyma showed a slow contrast agent accumulation and clearly increased HU data between 3 and 7 hours after injection. No significant renal parenchymal enhancement or excretion was noticed. At early time points after administration, DHOG exhibits characteristics of a macromolecular contrast agent by demonstrating a blood pool effect. At later time points, DHOG provides a prolonged, marked liver enhancement on microCT images due to its specific liver uptake. For a lesion size of 1 mm diameter, the variability in between two scans was 27.7 HU (P < .05) and the variability for different planes of one scan was 19.8 HU (P < .05). DHOG yields a very good visualization of the liver and delineation of the surrounding structures with a long plateau. It is a very suitable contrast agent for liver imaging in mice for microCT imaging. The presented protocol provides a high reproducibility for lesion detection with a relatively low radiation dose.

Development of a tumor-targeting MR contrast agent using the high-affinity folate receptor: work in progress.

Macromolecular contrast agents enhance tumors by means of active or passive targeting. Active targeting requires surface receptors. Many tumors of epithelial origin express the high-affinity folate receptor (hFR), including ovarian tumors. The objective of this research was to enhance tumors that express hFR using macromolecular contrast agents conjugated to folic acid. The authors prepared a folate-conjugated dendrimer polychelate by attaching folic acid to a fourth-generation ammonia-core polyamidoamine dendrimer. The remaining amines were reacted with 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriamine pentaacetic acid. Relaxivity measurements (r1 and r2) and MRI were conducted at 4.7 T. The dendrimer r2 exceeded that of Gd-HP-DO3A by 8.2 times at 4.7 T. It increased the tumor percentage contrast enhancement, 24 hours after injection, of T2-weighted images by 33%. This new agent accumulates in tumors expressing hFR. These results do not differentiate between active and passive targeting mechanisms. Receptor-negative tumors suggest a mechanism other than a nonspecific blood pool effect.

Superparamagnetic iron oxide enhanced MR angiography of the portal vein system

Superparamagnetic iron oxide (SPIO) is used for the detection of focal liver lesions. The current study examines whether the blood-pool effect of an approved substance is adequate for contrast-enhanced MR angiography of the portal venous system. Fifteen patients [9 women, 6 men, mean age 57 (34-73)] were examined with a breathhold 3D-FISP sequence (TR/TE/FA; 5 ms/2 ms/25 degrees) at 1.5 Tesla (Vision; Siemens, Erlangen) during the last third of a half-hour Infusion of a standard dose (15 mumol Fe/kg) of AMI-25 (Endorem, Guerbet Co., France). The image quality of source images and 3D reconstructions was evaluated by two examiners using a 3-point scale. Large vessels (portal vein, left and right branch of the portal vein, superior mesenteric vein, splenic vein) are visualized well or adequately in 80-93% of the cases, while this was achieved in only 53-60% of the small veins (vessels of the first order emptying into the superior mesenteric vein and the spleen). Venous arcades of the mesenterium are not visible by this technique. SPIO-supported MRA of the portal venous system yields usable results in the majority of patients. A possible indication is preinterventional angiography together with an SPIO examination for the detection of focal liver lesions.

Venous uptake of 99Tcm-MIBI during resting cardiac imaging: incidence and the effect of using a flush

99Tcm-methoxy-isobutyl-isonitrile (99Tcm-MIBI) is taken up by the vein through which it is injected in some individuals. We prospectively analysed technical and clinical factors that may be associated with this uptake. Imaging was performed over 1 h after injection so excluding a blood pool effect. The frequency of uptake could be reduced from 25.9% to 4.2% by using a 20 ml saline flush (p < 0.05). Other factors appeared irrelevant. The presence of venous uptake did not affect myocardial counting statistics but, if unrecognized, it could cause confusion in studies of the neck or chest that use 99Tcm-MIBI.

Radiolabelled white blood cell imaging in arthritis. Is it a blood pool effect?

The aim of this study is to determine whether white blood cell imaging in inflammatory conditions is due to a blood pool effect as a result of an increased vascularity and vascular permeability, or whether cellular migration is the major contributing factor. It will be shown that white cell uptake is a specific phenomenon in the rheumatoid knee joint and not just a blood pool effect.

5. Radiolabelled white blood cell imaging. Is it a blood pool effect?

Departments of Nuclear Medicine, Royal Liverpool Hospital, Liverpool and St Bartholomew's Hospital, London