Hemodynamic assessment of celiaco-mesenteric anastomosis in patients with pancreaticoduodenal artery aneurysm concomitant with celiac artery occlusion using flow-sensitive four-dimensional magnetic resonance imaging.

OBJECTIVES: Many pancreaticoduodenal artery (PDA) aneurysms are associated with celiac artery (CA) stenosis. The pathogenesis of PDA aneurysm may be associated with hemodynamic changes due to CA stenosis/occlusion. The aim of this study was to assess the hemodynamic changes of celiaco-mesenteric anastomosis in patients with PDA aneurysms concomitant with CA occlusion using four-dimensional flow-sensitive magnetic resonance imaging (4D-Flow). METHODS: 4D-Flow was performed preoperatively on five patients. Seven age- and sex-matched individuals were used as controls. Hemodynamic parameters such as flow volume and maximum flow velocity in PDAs, gastroduodenal arteries, common hepatic arteries, and superior mesenteric arteries were compared between both groups. Wall shear stress (WSS) and oscillatory shear index (OSI) were mapped in both groups. RESULTS: In the patient group, 4D-Flow identified retrograde flow of both gastroduodenal arteries and common hepatic arteries. Heterogeneous distribution patterns of both WSS and OSI were identified across the entire PDA in the patient group. OSI mapping showed multiple regions with extremely high OSI values (OSI > 0.3) in all patients. All PDA aneurysms, which were surgically resected, were atherosclerotic. CONCLUSIONS: 4D-Flow identified hemodynamic changes in celiaco-mesenteric arteries in patients with PDA aneurysms with concomitant CA occlusion. These hemodynamic changes may be associated with PDA aneurysm formation.

Functional assessment of pancreatic parenchyma after secretin administration using serial T2-weighted echo-planar magnetic resonance imaging.

Signal intensity (SI) changes of pancreatic parenchyma were evaluated after intravenous administration of secretin using T2-weighted single-shot spin-echo echo-planar imaging (EPI) to assess this method as a magnetic resonance (MR) test of pancreatic exocrine function. Nine volunteers were studied with serial single-shot EPI of the pancreas for 15 minutes after the injection of secretin or saline. The normal pattern of pancreatic SI change was demonstrated after intravenous injection of secretin, a single peak at 3-4 minutes in the head, body, and tail, followed by a gradual decrease in SI. Saline injection did not induce a significant SI change. There was no statistical difference in the peak contrast ratios (first mean, 1.21-1.25, vs. second mean, 1.18-1.22) and peak times (first mean, 3.2-3.7 minutes, vs. second mean, 3.1-3.6) in a repeat study. By evaluating the pattern of time-response curves obtained from serial T2-weighted EPI after secretin injection, pancreatic exocrine function may be directly assessed at the level of the head, body, and tail.

Assessment of gadolinium-enhanced time-resolved three-dimensional MR angiography for evaluating renal artery stenosis.

OBJECTIVE: The purpose of this study was to assess the image quality of gadolinium-enhanced time-resolved three-dimensional (3D) MR angiography and to evaluate its accuracy in revealing renal artery stenosis. SUBJECTS AND METHODS: Thirty-nine patients underwent MR angiography using an ultrafast 3D Fourier transform spoiled gradient-recalled acquisition in the steady state (TR/TE range, 2.6/0.7--0.8). Five seconds after administration of 15--20 mL gadodiamide hydrate, four or five consecutive data sets with imaging times of 7.0--7.6 sec were acquired during a single breath-hold. A timing examination was not performed. Image quality was assessed using quantitative analysis (signal-to-noise, contrast-to-noise, and venous-to-arterial enhancement ratios) and qualitative analysis (presence of venous overlap, presence of artifacts, and degree of renal arterial enhancement). MR angiography depiction of the renal artery stenosis was evaluated using conventional angiography as the standard of reference. RESULTS: On the best arterial phase, average aortic signal-to-noise ratio (+/-SD) was 74.5 +/- 24.4, aorta-to--inferior vena cava contrast-to-noise ratio was 70.8 +/- 23.4, and inferior vena cava--to-aorta venous-to-arterial enhancement ratio was 0.03 +/- 0.04. No venous overlap was seen in 38 of 39 patients. Substantial enhancement of renal arteries was seen in all patients without any noticeable artifacts. MR angiography correctly depicted the degree of stenosis in 44 of 47 normal arteries, 13 of 16 mildly stenotic arteries, five of five moderately stenotic arteries, three of four severely stenotic arteries, and one of one occluded artery. Sensitivity and specificity for revealing greater than 50% stenosis was 100%. CONCLUSION: Time-resolved 3D MR angiography can provide high-quality arteriograms. Its performance in revealing renal artery stenosis is comparable with that of conventional angiography.

Assessment of the radiochemical design of antibodies with a metabolizable linkage for target-selective radioactivity delivery.

Interposition of a metabolizable linkage has been performed to reduce the hepatic radioactivity levels of radiolabeled antibodies. To estimate the validity of this strategy, a radioiodination reagent (HML) that provides a stable attachment for m-iodohippuric acid with proteins in plasma while facilitating rapid and selective release of the compound after lysosomal proteolysis in the liver was conjugated with a monoclonal antibody (mAb) against osteogenic sarcoma (OST7, IgG1). Radiolabeled OST7 conjugates with a plasma-labile ester bond for releasing m-iodohippuric acid (MIH), plasma-stable amide bonds for releasing radiometabolites of hepatobiliary excretion (MPH), or slow elimination rates from hepatocytes ([111In]EMCS-Bz-EDTA) were prepared with similar conjugation chemistry. The four radiolabeled OST7 conjugates were characterized both in vitro and in vivo. All the radiolabeled OST7 conjugates had similar radiochromatograms on size-exclusion HPLC and similar antigen binding affinities. While MIH-OST7 indicated accelerated clearance of radioactivity from the blood due to the release of m-iodohippurate, the rest of the three radiolabeled OST7 conjugates remained stable in serum incubation studies and had similar radioactivity elimination from the blood in vivo. When injected into normal mice, HML-OST7 demonstrated tissue-to-blood ratios of radioactivity similar to those of MIH-OST7 and significantly lower than those of the other two radiolabeled OST7 conjugates. In biodistribution studies in nude mice, both HML-OST7 and MIH-OST7 exhibited tumor-to-liver or tumor-to-intestine ratios of radioactivity higher than those of [111In]EMCS-Bz-EDTA-OST7 or MPH-OST7, respectively. HML-OST7, MPH-OST7, and [111In]EMCS-Bz-EDTA-OST7 indicated there were no changes in the radioactivity levels in the tumor between 24 and 48 h postinjection, whereas MIH-OST7 significantly decreased the radioactivity levels in the tumor at these time points. HML reduced the radioactivity levels in nontarget tissues without impairing the tumor radioactivity levels delivered by OST7. These findings indicated that the design of a radiolabeled mAb that is stable in plasma and liberates the radiometabolite of rapid urinary excretion constitutes an effective strategy for achieving target-selective radioactivity delivery.

Assessment of radiochemical design of antibodies using an ester bond as the metabolizable linkage: evaluation of maleimidoethyl 3-(tri-n-butylstannyl)hippurate as a radioiodination reagent of antibodies for diagnostic and therapeutic applications.

Reduction of radioactivity levels in nontarget tissues such as the liver and kidney constitutes a problem to be resolved in diagnostic and therapeutic applications of radiolabeled monoclonal antibodies (mAbs). A new radioiodination reagent with an ester bond to liberate m-iodohippuric acid from covalently conjugated proteins, maleimidoethyl 3-(tri-n-butylstannyl)hippurate (MIH), was recently developed. MIH liberated m-iodohippuric acid from galactosylneoglycoalbumin in murine liver, and the radiometabolite was rapidly eliminated from the liver into urine as an intact structure. In this study, intact IgG and Fab fragment of a mAb against osteogenic sarcoma were radioiodinated with MIH to further assess the applicability of MIH to radioimmunoimaging and therapy. For comparison, a mAb radioiodinated with N-succinimidyl iodobenzoate (SIB) and indium-111 (111In)-labeled mAbs with diethylenetriaminepentaacetic dianhydride (cDTPA) or 1-[4-[(5-maleimidopentyl)amino]benzyl]-ethylenediaminetetraacetic acid (EMCS-Bz-EDTA) were used. Size-exclusion HPLC analysis and cell binding assays indicated the preservation of both structure and antigen binding affinity of radioiodinated MIH-OST7 (IgG). In biodistribution studies in mice, [125I]MIH-OST7 (IgG) showed faster systemic clearance of radioactivity after 24 h postinjection than did [131I]SIB- and [111In]EMCS-Bz-EDTA-OST7 (IgG). [125I]MIH-OST7 (IgG) also exhibited much lower radioactivity levels in nontarget tissues such as the liver and kidney, with higher radioactivity levels in the blood up to 72 h postinjection when compared with [111In]cDTPA-OST7 (IgG). Radioactivity excreted from the mice was found in the urine as m-iodohippuric acid, following administration of [125I]MIH-OST7 (IgG). In athymic mice bearing osteogenic sarcoma, [131I]MIH-OST7 (IgG) indicated higher tumor-to-nontarget ratios of radioactivity at both 24 and 48 h postinjection than [125I]SIB-OST7 (IgG). Although both radioiodinated OST7s showed similar radioactivity levels in the target at 24 h postinjection, a small but significant decrease in the target radioactivity level was observed with [131I]MIH-OST7 (IgG) at 48 h postinjection. In addition, [131I]MIH-OST7 (Fab) showed very rapid cleavage of the ester bond both in vivo and in vitro. These findings indicated that while MIH may be a useful reagent for radioimmunoimaging using IgG, mAb, its application to smaller molecular weight mAbs and radioimmunotherapy would be hindered due to the labile characteristics of the ester bond in plasma. Thus, while the present study reinforced the usefulness of metabolizable linkages for reducing nontarget radioactivity levels, a development of plasma-stable metabolizable linkages is also warranted for radioimmunotherapy and for smaller molecular weight polypeptides.