technetium-tc-99m-tetrofosmin and Ischemia

Peripheral arterial disease (PAD) is an atherosclerotic occlusive disease of the non-coronary vessels that is characterized by lower extremity tissue ischemia, claudication, increased prevalence of lower extremity wounds and amputations, and impaired quality of life. Critical limb ischemia (CLI) represents the severe stage of PAD and is associated with additional risk for wound formation, amputation, and premature death. Standard clinical tools utilized for assessing PAD and CLI primarily focus on anatomical evaluation of peripheral vascular lesions or hemodynamic assessment of the peripheral circulation. Evaluation of underlying pathophysiology has traditionally been achieved by radiotracer-based imaging, with many clinical investigations focusing on imaging of skeletal muscle perfusion and cases of foot infection/inflammation such as osteomyelitis and Charcot neuropathic osteoarthropathy. As advancements in hybrid imaging systems and radiotracers continue to evolve, opportunities for molecular imaging of PAD and CLI are also emerging that may offer novel insight into associated complications such as peripheral atherosclerosis, alterations in skeletal muscle metabolism, and peripheral neuropathy. This review summarizes the pros and cons of radiotracer-based techniques that have been utilized in the clinical environment for evaluating lower extremity ischemia and common pathologies associated with PAD and CLI.

Topics: Foot; Humans; Inflammation; Ischemia; Muscle, Skeletal; Organophosphorus Compounds; Organotechnetium Compounds; Osteomyelitis; Perfusion; Peripheral Arterial Disease; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography

Angiogenesis involves the interplay of endothelial progenitor cells, pericytes, growth factors, and cellular matrix components. The use of mesenchymal stem cells, which are closely related to pericytes and produce diverse angiogenic growth factors and matrix molecules, seems to be a promising therapeutic modality. We postulate that the use of a combination cell product (mesenchymal stem cells in conjunction with a source of endothelial progenitor cells) is safe and efficient and may optimize the clinical results obtained with the use of endothelial progenitor cells alone. This study assessed whether the intramuscular infusion of a combination cell product represents a viable, effective, and lasting therapeutic modality to improve perfusion in severely ischemic limbs.. Patients with limb ischemia (n=26) received an intramuscular (gastrocnemius) infusion of the combination cell product in the most ischemic leg and a placebo product in the (less ischemic) contralateral leg. Clinical follow-up (months 0.5, 1, 2, and 4 postinfusion) included evaluation of pain-free walking time, ankle-brachial index, perfusion scintigraphy, and quality of life survey.. No adverse events occurred after infusion. Efficacy assessment indicated that after cell infusion there was a significant improvement in walking time and ankle-brachial index. In addition, technetium-99m-tetrofosmin scintigraphy demonstrated a significant increase of perfusion in the treated limbs compared with the respective control legs.. This phase II clinical trial shows that the use of a combination cell therapy is safe and effective in increasing blood flow in the ischemic legs of patients with limb ischemia.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Cell- and Tissue-Based Therapy; Female; Foot Ulcer; Humans; Ischemia; Leg; Male; Mesenchymal Stem Cells; Middle Aged; Monocytes; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Quality of Life; Radionuclide Imaging; Radiopharmaceuticals; Regional Blood Flow

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis.

Topics: Animals; Disease Models, Animal; Fluorescent Dyes; Hindlimb; Ischemia; Mice; Microscopy, Confocal; Multimodal Imaging; Neovascularization, Physiologic; Oligopeptides; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Rhodamines; Technetium; Tissue Distribution

Cadmium zinc telluride (CZT) detectors with linear counting rate response enable count subtraction in sequential scanning. We evaluated whether count subtraction eliminated the need for higher activity doses in the second part of the 1-d stress-rest myocardial perfusion imaging (MPI) protocol.. For 50 patients (mean age ± SD, 66 ± 12 y) with visually abnormal (n = 42) or equivocal (n = 8) adenosine-stress MPI (320 MBq of (99m)Tc-tetrofosmin) on a CZT camera, rest MPI was performed with a low dose (320 MBq) and repeated after injection of an additional 640 MBq of (99m)Tc-tetrofosmin to achieve a standard 3-fold increased dose at rest (960 MBq), compared with stress (320 MBq). Low-dose rest myocardial perfusion images were reconstructed after subtracting the background activity of the preceding stress scan. Segmental percentage tracer uptake of the 2 rest myocardial perfusion images (320 vs. 960 MBq) was compared using intraclass correlation and Bland-Altman limits of agreement. Patient- and coronary territory-based clinical agreement was assessed.. The standard protocol revealed ischemia in 34 (68%) and a fixed defect in 8 (16%) patients, of whom 33 (97%) and 8 (100%) were correctly identified by low-dose MPI (clinical agreement, 98%). Segmental uptake correlated well between low- and standard-dose rest scans (r = 0.94, P < 0.001; Bland-Altman limits of agreement, -11 to +11%). Defect extent was 14.4% (low-dose) versus 13.1% (standard-dose) at rest (P = not statistically significant) and 26.6% at stress (P < 0.001 vs. rest scans).. These promising results suggest that accurate assessment of ischemic myocardial disease is feasible with a low-dose-low-dose 1-d SPECT MPI protocol using a CZT device.

Topics: Adult; Aged; Aged, 80 and over; Cadmium; Female; Humans; Image Processing, Computer-Assisted; Ischemia; Male; Middle Aged; Myocardial Perfusion Imaging; Organophosphorus Compounds; Organotechnetium Compounds; Phantoms, Imaging; Radiopharmaceuticals; Semiconductors; Tellurium; Tomography, Emission-Computed, Single-Photon; Zinc

We investigated whether myocardial perfusion imaging (MPI) can demonstrate the effect of classical preconditioning.. 21 patients with documented coronary artery disease (stenosis>or=70%) underwent two exercise stress tests (EST) with concomitant MPI, using TL-201 for the first and tetrofosmin-Tc-99m for the second. A third MPI was performed at rest, using Tc-99m. Total defect score was derived by summing tracer uptake in a 17 segments left ventricle model, graded on a 5-point scale. Tomographic images were also analyzed quantitatively, to derive the total defect size.. Maximum ST depression did not differ significantly between the two EST (2.2+/-1 vs 2.2+/-1 mm, p=NS), however in the second EST longer times for onset of ischemic changes (228+/-94 vs 265+/-103 s, p=0.01) and appearance of angina (282+/-153 vs 328+/-177 s, p=0.04) were observed. Exercise perfusion abnormalities were significantly lower in the second MPI, in terms of both total defect score (19.2+/-11.5 vs 10+/-10.4, p<0.0001) and total defect size (28.3+/-16.9 vs 13.8+/-15.8, p<0.0001).. Significant improvement in perfusion pattern was demonstrated in the second MPI, accompanied by delayed appearance of ischemic manifestations. The improvement in myocardial perfusion extends far beyond the changes that can be attributed to differences in myocardial uptake between tracers, reflecting the effect of classical preconditioning.

Topics: Aged; Coronary Artery Disease; Exercise Test; Female; Heart Ventricles; Humans; Ischemia; Ischemic Preconditioning; Male; Middle Aged; Myocardial Ischemia; Organophosphorus Compounds; Organotechnetium Compounds; Perfusion; Time Factors

Topics: Aged; Diagnosis, Differential; Female; Hernia, Hiatal; Humans; Ischemia; Kidney Failure, Chronic; Myocardium; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Twenty-one patients with arteriosclerosis obliterans (ASO) were studied with 99mTc-tetrofosmin exercise leg perfusion scintigraphy using the delayed administration method. In this method, tracer was injected 4 minutes after termination of symptom-limited repetitive climbing of a stair to validate prolonged vasodilatation in an ischemic lower limb after exercise. Visual and quantitative analyses were performed to evaluate a diseased leg using dynamic and static images. On a posterior whole body image, all cases except one showed decreased foot uptake in the affected side (affected normal ratio; ANR = 0.82 +/- 0.14). On dynamic images, 9 cases showed transient hyper-accumulation (blush phenomenon) only in the thigh of the affected side suggesting that this valuable finding may be a useful diagnostic sign to distinguish a diseased leg. Sensitivity and positive predictive value were 71.4% and 93.8% to detect a diseased leg based on more than one finding of non-visualization of ilio-femoral artery, muscle-soft tissue blush, and early venous return in a dynamic study. Moreover, a low uptake of ANR of below 0.90 in the foot in the static study gave an improved sensitivity of 85.7%. The transit time of the diseased legs (12.0 +/- 3.1 sec.) which was determined as the interval between the time of arterial and venous peak counts was significantly shorter than that of normal legs (17.3 +/- 4.5 sec.; p < 0.0001, paired t-test). The cases with blush phenomenon showed significantly higher thigh ANR (1.04 +/- 0.11) than those without (0.94 +/- 0.08; p < 0.05, unpaired t-test). These results could reflect prolongation of a hypervascular state after exercise in a diseased leg which sometimes induced blush phenomenon at arterial phase and high leg uptake at static phase. This scintigraphy is useful for the detection of a diseased leg as well as for grasping changes of vascular regulation after stress in patients with ASO.

Topics: Aged; Aged, 80 and over; Arteriosclerosis Obliterans; Exercise Test; Female; Humans; Ischemia; Leg; Male; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals