DNA double-strand breaks in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy.

OBJECTIVES: To investigate DNA double-strand breaks (DSBs) in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy (MPS) using y-H2AX immunofluorescence microscopy and to correlate the results with 99mTc activity in blood samples. METHODS: Eleven patients who underwent two-day MPS were included. DSB blood sampling was performed before and 5min, 1h and 24h after the first and second radiotracer injections. 99mTc activity was measured in each blood sample. For immunofluorescence microscopy, distinct foci representing DSBs were quantified in lymphocytes after staining for the phosphorylated histone variant y-H2AX. RESULTS: The 99mTc-MIBI activity measured on days one and two was similar (254±25 and 258±27 MBq; p=0.594). Compared with baseline DSB foci (0.09±0.05/cell), a significant increase was found at 5min (0.19±0.04/cell) and 1h (0.18±0.04/cell) after the first injection and at 5min and 1h after the second injection (0.21±0.03 and 0.19±0.04/cell, respectively; p=0.003 for both). At 24h after the first and second injections, the number of DSB foci had returned to baseline (0.06±0.02 and 0.12±0.05/cell, respectively). 99mTc activity levels in peripheral blood samples correlated well with DSB counts (r=0.451). CONCLUSIONS: DSB counts reflect 99mTc-MIBI activity after injection for two-day MPS, and might allow individual monitoring of biological effects of cardiac nuclear imaging. KEY POINTS: • Myocardial perfusion scintigraphy using 99mTc induces time-dependent double-strand breaks (DSBs) • γ-H2AX immunofluorescence microscopy shows DSB as an early response to radiotracer injection • Activity measurements of 99mTc correlate well with detected DSB • DSB foci induced by 99mTc return to baseline 24h after radiotracer injection.

Effects of adenosine and a selective A2A adenosine receptor agonist on hemodynamic and thallium-201 and technetium-99m-sestaMIBI biodistribution and kinetics.

OBJECTIVES: The purpose of this study was to compare a selective A(2A) adenosine receptor agonist (regadenoson) with adenosine in clinically relevant canine models with regard to effects on hemodynamics and thallium-201 ((201)Tl) and technetium-99m ((99m)Tc)-sestaMIBI biodistribution and kinetics. BACKGROUND: The clinical application of vasodilator stress for perfusion imaging requires consideration of the effects of these vasodilating agents on systemic hemodynamics, coronary flow, and radiotracer uptake and clearance kinetics. METHODS: Sequential imaging and arterial blood sampling was performed on control, anesthetized closed-chest canines (n = 7) to evaluate radiotracer biodistribution and kinetics after either a bolus administration of regadenoson (2.5 microg/kg) or 4.5-min infusion of adenosine (280 microg/kg). The effects of regadenoson on coronary flow and myocardial radiotracer uptake were then evaluated in an open-chest canine model of a critical stenosis (n = 7). Results from ex vivo single-photon emission computed tomography were compared with tissue well-counting. RESULTS: The use of regadenoson compared favorably with adenosine in regard to the duration and magnitude of the hemodynamic effects and the effect on (201)Tl and (99m)Tc-sestaMIBI biodistribution and kinetics. The arterial blood clearance half-time was significantly faster for (99m)Tc-sestaMIBI (regadenoson: 1.4 +/- 0.03 min; adenosine: 1.5 +/- 0.08 min) than for (201)Tl (regadenoson: 2.5 +/- 0.16 min, p < 0.01; adenosine: 2.7 +/- 0.04 min, p < 0.01) for both vasodilator stressors. The relative microsphere flow deficit (0.34 +/- 0.02%) during regadenoson stress was significantly greater than the relative perfusion defect with (99m)Tc-sestaMIBI (0.69 +/- 0.03%, p < 0.001) or (201)Tl (0.53 +/- 0.02%, p < 0.001), although (201)Tl tracked the flow deficit within the ischemic region better than (99m)Tc-sestaMIBI. The perfusion defect score was larger with (201)Tl (22 +/- 2.8% left ventricular) than with (99m)Tc-sestaMIBI (17 +/- 1.7% left ventricular, p < 0.05) on ex vivo single-photon emission computed tomography images. CONCLUSIONS: The bolus administration of regadenoson produced a hyperemic response comparable to a standard infusion of adenosine. The biodistribution and clearance of both (201)Tl and (99m)Tc-sestaMIBI during regadenoson were similar to adenosine vasodilation. Ex vivo perfusion images under the most ideal conditions permitted detection of a critical stenosis, although (201)Tl offered significant advantages over (99m)Tc-sestaMIBI for perfusion imaging during regadenoson vasodilator stress.

99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with 99mTc-sestamibi and 99mTc-tetrofosmin in rats.

UNLABELLED: (99m)Tc-[bis (dimethoxypropylphosphinoethyl)-ethoxyethylamine (PNP5)]-[bis (N-ethoxyethyl)-dithiocarbamato (DBODC)] nitride (N-PNP5-DBODC or N-DBODC5) is a new monocationic myocardial perfusion tracer. We sought to compare the myocardial uptake and clearance kinetics and organ biodistribution of (99m)Tc-N-DBODC5 with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. METHODS: Seventy-five anesthetized Sprague-Dawley rats were injected intravenously with 22.2-29.6 MBq (99m)Tc-N-DBODC5 (n = 25), (99m)Tc-sestamibi (n = 25), or (99m)Tc-tetrofosmin (n = 25). Rats were euthanized at either 2, 10, 20, 30, or 60 min after injection and gamma-well counting was performed on excised organ (heart, lung, and liver) and blood samples. In 3 additional rats, serial in vivo whole-body gamma-camera imaging with each tracer was performed. RESULTS: (99m)Tc-N-DBODC5 cleared rapidly from the blood pool. At 2 min after injection, (99m)Tc-N-DBODC5 blood activity was significantly lower than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin (P < 0.01) and remained lower over 60 min. Myocardial (99m)Tc-N-DBODC5 uptake was rapid (2.9% +/- 0.1% injected dose/g at 2 min), and there was no significant clearance over 60 min, similar to (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. All 3 tracers exhibited rapid lung clearance. Importantly, (99m)Tc-N-DBODC5 cleared more rapidly from the liver than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin. As early as 30 min after injection, (99m)Tc-N-DBODC5 heart-to-liver ratio was 5.7 +/- 1.0 versus 1.6 +/- 0.1 and 2.9 +/- 0.3 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P < 0.05). By 60 min, (99m)Tc-N-DBODC5 heart-to-liver ratio further increased to 18.4 +/- 2.0 compared with 2.6 +/- 0.2 and 5.8 +/- 0.7 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P < 0.001). The rapid blood pool, lung, and liver clearance of (99m)Tc-N-DBODC5 resulted in excellent-quality myocardial images within 30 min after injection. CONCLUSION: (99m)Tc-N-DBODC5 is a promising new myocardial perfusion tracer with superior biodistribution properties. The rapid (99m)Tc-N-DBODC5 liver clearance may shorten the duration of imaging protocols by allowing earlier image acquisition and may markedly reduce the problem of photon scatter from the liver into the inferoapical wall on myocardial images.

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion.

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.

Comparison of 99mTc-MIBI uptakes on planar images with those in excised rats organs.

The precision with which images reflect tracer uptake in the myocardium has been studied. Additionally, the degree to which Tc methoxyisobutylisonitrile (99mTc-MIBI) in the liver gave the effect to a myocardial image has been examined. After administering Tc-MIBI to normal male rats, we compared the myocardial uptakes obtained using a gamma camera with the actual uptakes in the excised organs. Twenty-nine rats were used. Following imaging, the anterior view at 5, 10, 15, 30, 45, 60, 90 and 120 min after administration of the tracer, uptakes in the heart, lung, liver and blood were estimated with a well-type scintillation counter (WC) and represented as the percentage of the injected dose per gram of tissue (%ID/g). The regions of interest (ROIs) were placed on planar images (PI) and the uptake in each organ was estimated as the percentage of the injected dose per pixel (%ID/pixel). The ratios of PI-to-WC and heart-to-organ were also evaluated. Cardiac uptake with WC was maximum (1.581%+/-1.893%) at 10 min post-injection. On the other hand, that with PI was maximum (1.493%+/-0.598%) at 45 min post-injection, but there were significant differences between both measurements (PI/WC ratio: about 1.0 time). Pulmonary uptake with WC was the maximum at 5 min (0.808%+/-0.015%) post-injection, and decreased gradually. PI measurement showed the maximum value at 45 min (0.760%+/-0.012%). Hepatic uptake with WC was the maximum at 30 min (0.594%+/-0.254%). On the other hand, PI measurement showed the same pattern with WC, but these values were higher value than WC as the whole. PI measurement showed higher uptakes in each organ than WC measurement. It was concluded that uptakes or the heart-to-organ ratio obtained clinically with PI might not represent a value that is always accurate.

Correlation of 99mTc-sestamibi uptake with blood-pool and osseous phase 99mTc-MDP uptake in malignant bone and soft-tissue tumours.

Technetium-99m-sestamibi (99mTc-MIBI) imaging is a well-established modality in oncologic investigations. The current study aimed to investigate whether any relationship could be found between 99mTc-MIBI uptake and local perfusion in malignant bone and soft-tissue tumours. It also aimed to compare 99mTc-MIBI images with those of technetium-99m-methylene diphosphonate (99mTc-MDP) bone scintigraphy with regard to the activity distribution pattern, intensity and lesion extension. The study group included 24 patients with various bone and soft-tissue tumours. Three-phase bone scintigraphy and 99mTc-MIBI studies were performed within the same week before any surgical and therapeutic intervention. Images were evaluated visually and quantitatively using regions of interest (ROIs) over the lesion and adjacent normal tissue. The 99mTc-MIBI study was positive with varying degrees of uptake (range, 1.4-5.3). The mean 99mTc-MIBI uptake and 99mTc-MDP blood-pool and osseous phase activity ratios were 2.5 +/- 0.5, 2.8 +/- 1.0 and 5.5 +/- 4.0, respectively. The correlation between the 99mTc-MIBI uptake and blood-pool ratios was 0.70 (P<0.05). While activity distribution patterns were in agreement in 99mTc-MIBI and blood-pool images in the majority of cases, 99mTc-MIBI better delineated tumour viability and extension in five cases. In conclusion, 99mTc-MIBI accumulation shows a reasonable correlation with blood-pool uptake assuming the presence of multifactorial mechanisms in addition to local hyperaemia. Better delineation of tumour outlines and cellular activity seems to be an advantage of 99mTc-MIBI scintigraphy which may be helpful in the evaluation of musculoskeletal tumours.