Myocardial Kinetics of a Putative Hypoxic Tissue Marker,
            <sup>99m</sup>
            Tc-Labeled Nitroimidazole (BMS-181321), After Regional Ischemia and Reperfusion

Stone, Charles K.; Mulnix, Timothy; Nickles, Robert J.; Renstrøm, Britta; Nellis, S. H.; Liedtke, A. J.; Nunn, Adrian D.; Kuczynski, Bruce L.; Rumsey, William L.

doi:10.1161/01.cir.92.5.1246

Cited by 20 publications

(7 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Although studies have suggested retention of these radiocompounds by ischemic myocardium, their use has been limited by extensive hepatic uptake, low cardiac specificity, and low target-to-background uptake of tracer. 1,25,26 For example, only 0.008% of an intracoronary injection of a 99m Tc-labeled nitroimidazole was retained per gram of ischemic porcine myocardium, 26 which is lower than the ischemic skeletal muscle retention of our intravenously injected VEGF 121 . This may be due in part to the threshold requirement of extremely low oxygen tensions before these compounds are retained.…”

Section: Comparison With Previous Studiesmentioning

confidence: 85%

See 1 more Smart Citation

Targeted In Vivo Labeling of Receptors for Vascular Endothelial Growth Factor

et al. 2003

View full text Add to dashboard Cite

Background— A method for identifying tissue experiencing hypoxic stress due to atherosclerotic vascular disease would be clinically useful. Vascular endothelial growth factor-121 (VEGF 121 ) is an angiogenic protein secreted in response to hypoxia that binds to VEGF receptors overexpressed by ischemic microvasculature. We tested the hypothesis that VEGF receptors could serve as markers for ischemic tissue and hence provide a target for imaging such tissue with radiolabeled human VEGF 121 . Methods and Results— A rabbit model of unilateral hindlimb ischemia was created by femoral artery excision (n=14). Control rabbits (n=5) underwent identical surgery without femoral excision. On postoperative day 10, rabbits were intravenously administered 100 μCi of 111 In-labeled recombinant human VEGF 121 , and biodistribution studies and planar imaging were conducted at 3, 24, and 48 hours. On postmortem gamma counting, there was greater accumulation of 111 In-labeled VEGF 121 in ischemic than in control tissue ( P <0.02). Differential uptake of isotope by ischemic muscle was not seen in rabbits injected with 125 I-labeled human serum albumin (n=6). Radioactivity imaged in hindlimb regions of interest was significantly higher in ischemic muscle than in sham-operated and contralateral nonoperated hindlimb at 3 hours ( P <0.02). Immunohistochemical staining confirmed upregulation of VEGF receptors in ischemic skeletal muscle. Conclusions— Identification of the ischemic state via targeted radiolabeling of hypoxia-induced angiogenic receptors is possible. This approach could be useful for monitoring the efficacy of revascularization strategies such as therapeutic angiogenesis.

show abstract

Section: Comparison With Previous Studiesmentioning

confidence: 85%

“…This may be due in part to the threshold requirement of extremely low oxygen tensions before these compounds are retained. 26 …”

Section: Comparison With Previous Studiesmentioning

confidence: 99%

Targeted In Vivo Labeling of Receptors for Vascular Endothelial Growth Factor

et al. 2003

View full text Add to dashboard Cite

show abstract

“…ROI analyses yielded an ischaemic H/Lu ratio of 1.7 for 99m TcO(BAT-NI); the corresponding ratios for HL91 [21] and for BMS-181321 [5] were approximately twofold higher. The ischaemic H/Li ratio of 99m TcO(BAT-NI) is comparable to that of HL91 [21] and at least twofold higher than reported for BMS-181321 [3,5]. The ischaemic tissue contrast of the 99m TcO(BAT) tracers on planar images does not seem ideal for clinical use.…”

Section: Discussionmentioning

confidence: 99%

“…The high costs and limited availability of positron emission tomography (PET) systems, however, have spurred the search for nitroimidazole derivatives suitable for labelling with single-photon emitters. The most widely investigated compound, 99m TcO(PnAO-1-(2-nitroimidazole)) (BMS-181321), was taken up in ischaemic myocardium in vivo [3,4,5]. However, the high hepatic uptake of this tracer has made its clinical use questionable [3].…”

Section: Introductionmentioning

confidence: 99%

99mTcO(BAT-NI), a novel nitroimidazole tracer: in vivo uptake studies in ischaemic myocardium

Hoffend

Linke

Mohammed

et al. 2003

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Myocardial perfusion single-photon emission tomography (SPET) performed with cationic technetium-99m complexes indicates ischaemic areas as cold lesions. By contrast, nitroimidazole derivatives labelled with fluorine-18 or (99m)Tc have recently shown promising results for hot spot imaging of ischaemic myocardium. This study evaluates (99m)TcO(BAT-NI), a new (99m)Tc complex comprising the nitroimidazole ligand, 2,10-dimercapto-2,10-dimethyl-4,8-diaza-6-[4-(2-nitroimidazolyl)butyl]undecane, in a low-flow in vivo model of myocardial ischaemia in thoracotomised rats. To elucidate the influence of the 2-nitroimidazole group on ischaemia-induced uptake, comparisons with ligand derivatives were performed where (a) the 2-nitro group was deleted [(99m)TcO(BAT-I)], (b) the 2-nitroimidazole functionality was replaced by a Br atom [(99m)TcO(BAT-Br)] and (c) the (99m)TcO(BAT) moiety was replaced by an iodine-125 iodophenoxybutyl ligand ((125)IP-NI). The radiolabelled compounds were i.v. injected 15 min after reducing resting myocardial blood flow by 50-60% and the uptake of radioactivity was assessed 90 min post injection. Autoradiography of left ventricular short-axis slices showed median uptake ratios of ischaemic/non-ischaemic myocardium (I/N) of 3.4, 4.5 and 3.4 for (99m)TcO(BAT-NI), (99m)TcO(BAT-I) and (99m)TcO(BAT-Br), respectively. In contrast, (125)IP-NI was not preferentially taken up by ischaemic myocardium. Accumulation of (99m)TcO(BAT-NI) in ischaemic heart regions was comparable to that in the liver. Biodistribution studies showed a median uptake of 0.65% ID/g of (99m)TcO(BAT-NI) in ischaemic tissue and an I/N of 3.3. On planar images of the thorax and upper abdomen the ischaemic hearts were visualised faintly; the median heart to lung count ratio for (99m)TcO(BAT-NI) was 1.7, and the median heart to liver count ratio was 1.0. We conclude that uptake of (99m)TcO(BAT-NI) in ischaemic myocardium does not depend on the nitroimidazole moiety but is intrinsic to the BAT complex. Clinical use of the (99m)TcO(BAT)-labelled tracers seems unlikely owing to their low uptake and their low ischaemic tissue contrast on planar images in vivo.

show abstract

“…Imidazoles can be labeled with 99m Tc and potentially used to localize in areas of low oxygen tension during severe ischemic episodes [26].Therefore, these agents may have a potential role in the evaluation of acute chest pain. Several experimental studies have shown significant regional uptake of investigational nitroimidazoles in areas of low flow and demand ischemia [27][28][29][30]. Further study of these agents will be necessary to assess the degree of ischemia necessary to produce a sufficient decrement in tissue oxygen tension and subsequent retention of tracer.…”

Section: Nitroimidazolesmentioning

confidence: 99%

Use of radionuclide imaging in acute coronary syndromes

Abbott

Wackers²

2003

Curr Cardiol Rep

View full text Add to dashboard Cite

The triage of patients presenting to the emergency department (ED) with acute chest pain is a diagnostic challenge. Radionuclide myocardial perfusion imaging has been shown to have favorable diagnostic and prognostic value in this setting, with an excellent early sensitivity to detect acute myocardial infarction (MI) not achieved by other testing modalities. A normal resting perfusion imaging study has been shown to have a negative predictive value of over 99% to exclude MI. Observational and randomized trials of both rest and stress imaging in the ED evaluation of patients with chest pain have demonstrated reductions in unnecessary hospitalizations and cost savings compared with routine care. Perfusion imaging has also been used in risk stratification after MI, and for measurement of infarct size to evaluate reperfusion therapies. Novel "hot spot" imaging radiopharmaceuticals that visualize infarction or ischemia are currently undergoing evaluation and hold promise for future imaging of acute coronary syndromes.

show abstract

Myocardial Kinetics of a Putative Hypoxic Tissue Marker, ^99m Tc-Labeled Nitroimidazole (BMS-181321), After Regional Ischemia and Reperfusion

Abstract: Thus, acute regional ischemia in these studies was visualized as an increase in retention of BMS-181321, suggesting its applicability in the imaging of clinical conditions of myocardial hypoperfusion.

Cited by 20 publications

References 12 publications

Targeted In Vivo Labeling of Receptors for Vascular Endothelial Growth Factor

Targeted In Vivo Labeling of Receptors for Vascular Endothelial Growth Factor

99mTcO(BAT-NI), a novel nitroimidazole tracer: in vivo uptake studies in ischaemic myocardium

Use of radionuclide imaging in acute coronary syndromes

Contact Info

Product

Resources

About

Myocardial Kinetics of a Putative Hypoxic Tissue Marker, 99m Tc-Labeled Nitroimidazole (BMS-181321), After Regional Ischemia and Reperfusion

Abstract: Thus, acute regional ischemia in these studies was visualized as an increase in retention of BMS-181321, suggesting its applicability in the imaging of clinical conditions of myocardial hypoperfusion.

Cited by 20 publications

References 12 publications

Targeted In Vivo Labeling of Receptors for Vascular Endothelial Growth Factor

Targeted In Vivo Labeling of Receptors for Vascular Endothelial Growth Factor

99mTcO(BAT-NI), a novel nitroimidazole tracer: in vivo uptake studies in ischaemic myocardium

Use of radionuclide imaging in acute coronary syndromes

Contact Info

Product

Resources

About

Myocardial Kinetics of a Putative Hypoxic Tissue Marker, ^99m Tc-Labeled Nitroimidazole (BMS-181321), After Regional Ischemia and Reperfusion