This first clinical prospective study was conducted to use of technetium-99m immunoglobulin G (99mTc-IgG) as compared with autologous 99mTc-red blood cells (RBC) in gated blood pool ventriculography. We studied 12 patients who referred to us for a possible diagnosis of liver hemangioma or infection. Six patients underwent gated planar blood pool (GPBP) acquisition using 99mTc-RBC and 6 GPBP acquisition using 99mTc-IgG. The use of 99mTc-IgG in cardiac blood pool studies provided comparable images to 99mTc-RBC. In conclusion, 99mTc-IgG, which is readily available and needs only a single injection, may be an attractive alternative to 99mTc-RBC for the estimation of various cardiac function parameters like left ventricular function

Amini, A.

Ansari, M.

Asli, I.N.

Assadi, M.

Barekat, M.

Jallalat, S.

Javadi, H.

Semnani, S.

English

Golestan University of Medical Sciences Repository

Hellenic Journal of Nuclear Medicine January - April 2011 www.nuclmed.gr0Abstract This first clinical prospective study was conducted to use of technetium-99m immu-noglobulin G (99mTc-IgG) as compared with autologous 99mTc-red blood cells (RBC) in gat-ed blood pool ventriculography. We studied 12 patients who referred to us for a possible diagnosis of liver hemangioma or infection. Six patients underwent gated planar blood pool (GPBP) acquisition using 99mTc-RBC and 6 GPBP acquisition using 99mTc-IgG. The use of 99mTc-IgG in cardiac blood pool studies provided comparable images to 99mTc-RBC. In conclusion, 99mTc-IgG, which is readily available and needs only a single injection, may be an attractive alternative to 99mTc-RBC for the estimation of various cardiac function parameters like left ventricular function . IntroductionL eft ventricular (LV) function and ejection fraction (EF) studied by radionuclidicor echocardiographic techniques have long been diagnostic factors associated with cardiac function [1-3]. However, echocardiographic investigations (ECHOC) may have poor reproducibility and be unable to diagnose some lesions like those in the endo-cardium and the apex [4, 5] and gated single photon emission tomography (GSPET) per-fusion studies may be difficult to identify lesions with marked hypoperfusion [6].Gated blood pool ventriculography (GBPV) is usually carried out by labeling autologous red blood cells (RBC) with 99mTc-RBC [7]. Practical drawbacks of the 99mTc-RBC technique time and labor and the necessary manipulations of blood samples with a possible risk of contamination [8]. A number of studies have tried to use other blood-pool agents in addi-tion to 99mTc-RBC [9-13]. This article presents the first clinical prospective study using 99mTc-gamma immunoglobu-lin (IgG) as compared with 99mTc-RBC in GBPV, by measuring organ activity ratios and image quality. Patients and methods The study population included 12 patients (7 men and 5 women mean age 59.92±8.07 years) who had been referred to us for possible diagnosis of liver hemangioma or infection (Table 1). None had symptoms of typical or atypical ischemic heart disease (IHD) such as chest pain, history of myocardial infarction (MI), congestive heart failure, arythmia or his-tory of coronary interventions such as catheterization or coronary angioplasty. Six patients underwent GBPV acquisition using 99mTc-RBC (Fig. 1), and the remaining six cases underwent GBPV with 99mTc-IgG (Fig. 2). This study complied with the declaration of Helsinki and was approved by the Institu-tional Ethics Committee of Golestan University of Medical Science. All patients signed a written fully informed consent.Technetium-99m-RBC labeling was carried out using a modified in vitro method (ex-vivo) [10, 14]. The radiopharmaceutical was administered by direct intravenous (i.v.) injection [15]. According to this technique, at least 10min after stannous chloride administration (0.5mg to 2mg), 2-3mL of blood is withdrawn from the subject into a containing 99mTcO-4 syringe, and then administered using separate venous access to that used for the stannous chlo-ride administration previously. More than 95% labeling efficiency was achieved by this direct technique. For 99mTc-IgG preparation, a human nonspecific polyclonal IgG solution Comparison of technetium-99m IgG with technetium-99mred blood cells labeling in cardiac blood-pool scintigraphy: a preliminary studyHell J Nucl Med 2011; 14(1): 30-33 Published on line: 26 March 2011Original Technical NoteHamid Javadi1MD,Isa NeshandarAsli2MD,Shahriar Semnani1MD,Sara Jallalat1MD,Mojtaba Ansari3 MD,Abdullatif Amini4MD,Maryam Barekat4MD,Majid Assadi4MD1. Golestan Research Center ofGastroenterology andHepatology(GRCGH), Golestan UniversityofMedicalSciences, Gorgan, Iran2.Department ofNuclearMedicine, TaleghaniHospitaland3Department ofNuclearMedicine,Emam Hossein Hospital,ShaheedBeheshtiUniversity ofMedicalSciences, Tehran, Iran4. ThePersian GulfNuclearMedicine Research Center,Bushehr University ofMedicalSciences, Bushehr,Iran***Keywords: Cardiac blood-poolscintigraphy-Technetium-99m IgG-Technetium-99m redblood cells- Left ventricular ejection frac- tion (LVEF)Correspondence address:The Persian Gulf NuclearMedicineResearch Center, The PersianGulf Biomedical SciencesInstitute, Boostan 19 Alley,Imam Khomeini Street,Bushehr, IranTel: 0098-771-2580169Fax: 0098-771-2541828E-mail: assadipoya@yahoo.com,asadi@bpums.ac.irReceived:28 October 2010Acceptedrevised:16January 2011•Hellenic Journal of Nuclear Medicine January - April 2011www.nuclmed.gr  1with a concentration of about 10mg/mL in 0.01 M phosphate buffered saline (PBS) of pH 7.4 was acquired. Protein con-centration was appraised by Lowry technique [16]. The IgG was reduced by reacting with a molar excess of 2-mecap-toethanol 2000:1 (2-ME:IgG) and was incubated for 30min at room temperature. The reduced solution was then purified by eluting through a 1×15cm sephadex G25 column, using nitrogen purged phosphate buffered saline (PBS) as mobile phase. Aliquots containing 1mg of reduced protein and 20μL of previously reconstituted solution with 5mL of saline were mixed, passed through a 0.22μ membrane filter and then fro-zen in -80°C. The frozen products were lyophilized for 48h, sealed under vaccum, and stored at 4°C until use. For 99mTc labeling, vials of lyophilized reduced IgG were reconstituted with 740MBq of 99mTcO-4 eluted from a 99Mo/99mTc generator (Atomic Energy Organization of Iran, Tehran, Iran) [16]. The total cost of each compound was approximately $60.Gated BPV images were obtained and processed with commercially available software. For LVEF assessment, an observer (H.J) delineated the initial LV contours at end sys-tole (ES) and end diastole (ED). Background (bg) region of interest (ROI) were also ac-quired by use of a 2 to 3 pixel-wide crescent-shaped region located about 2 pixels far from the posterolateral wall. After the subtraction of a bg region surrounding the LV, EF was calculated by following formula:EF(%) = [(ED counts - ES counts)/ED counts] * 100.In addition, activities within the aforementioned bg region and the ED image of the LV were calculated and expressed in counts per pixel (c/p) to determine the LV/bg ratio.In order to evaluate the activity ratios in different organs, regions of interest (ROI) were manually drawn over the LV, right ventricle (RV), right lung, left lung, aorta, liver, and spleen on the static anterior datasets at 20min (early) and at 180min (delayed) post injection of 99mTc-RBC (Fig. 1) and of 99mTc-IgG (Fig. 2). These ROI also were expressed in c/p. The c/p ratios between early and delayed views were compared for each ROI. Image quality was also blindly assessed by two observers (M.M and M.A) using as criteria the simplicity of outlying the ED and ES, LV edges. Quality was classified as good, mild, or poor for both radiotracers. The data were expressed as mean±standard deviation (±SD); the Mann–Whitney U test was applied for quantitative comparison, and differences in proportion (categorical variables) were assessed by the chi-square test. A P value of <0.05 was considered statistically significant. ResultsNone of the patients had any adverse reactions such as nausea, flushing, coughing, dyspnea, muscle cramps or diz-ziness after the i.v. injection of 99mTc-IgG. The mean acquisi-tion times following injection of each radiotracer are shown in Table 1. Observers 1 and 2 based upon image qualities considered both radiotracers as of good quality for all par-ticipants. The demographic data and GBPV parameters in-cluding mean count/frame, EF, peak filling rate–end diastolic volume per second(PFR-EDV/S), peak filling rate (PFR), peak emptying rate (PFR)– EDV/sec, PER and LV/BKG between the two groups were not statistically different (Table 1).A contrast analysis of both compounds was carried out in terms of organ c/p ratios between early and delayed images. The mean c/p of the LV and the RV to the bg ratios on early and delayed views in patients with 99mTc-IgG were greater, relative to patients who had been tested with radiolabeled 99mTc-RBC (Table 2). The ten (as shown in Table 2) ratios in the early and delayed views between the two radiotracers were not significantly different (P value>0.05).In addition, organ ROI c/p was compared with respect to the biodistribution of the two radiopharmaceuticals over time by subtracting ROI c/p of early acquired, from delayed ROI of the static images. This comparison showed that the washout rate of 99mTc-IgG relative to 99mTc-RBC was not sig-nificantly different (Fig. 3). Original Technical NoteTable 1. The main characteristics and results of the two groups studiedRadiopharmaceutical 99mTc-RBC 99mTc-IgG P valueAge (year) 62.00± 8.87 57.83±7.36 0.37Male/Female 4/2 3/3 0.55Post injection time of acquisition (min.) 75.83±11.75 80.00±7.09 0.63Mean count/frame 326.50±187.30 424.17±239.81 0.42EF (%) 59.00±7.64 58.33±16.03 0.52PFR-EDV/S 3.20 ±0.77 2.49±0.62 0.15PFR (ms) 459.50 ±39.09 491.33±49.84 0.15PER-EDV/S -3.02±0.51 -2.62±0.74 0.15PER(ms) 97.00±20.74 112.00±21.53 0.15LV/BKG 2.55±0.99 2.11±0.78 0.52EF, ejection fraction; PFR-EDV/S, peak filling rate–end diastolic volume per second; PFR (ms), peak filling rate in millisecond; PER-EDV/S, peak emptying rate–end diastolic volume second; PER(ms), peak emptying rate in millisecond; LV/BKG, left ventricle/ bg.Hellenic Journal of Nuclear Medicine January - April 2011 www.nuclmed.gr2Figure 3. Comparison of the biodistribution of both radiopharmaceuticals by using c/p of ROI in different organs between early and delayed images. For this purpose, activities of early acquired ROI were subtracted from delayed ROI views of the static images.DiscussionDespite the advantages of planar GBPV, there are limita-tions, such as operator-dependent variability in determin-ing the best septal view and underestimation of the LVEF in anterior and inferior myocardial infarction, which are over-come by the SPET mode [17, 18].The LV and RV activity divided to bg did not differ between the two agents, so the blood pool images with 99mTc-IgG may be adequate for clinical application. Other 99mTc-labeled agents, such as human serum albu-min (99mTc-HSA) [10], diethylen triamine penta acetic-human serum albumin (DTPA-HSA) [11], and bis diethylphosphi-noethane bis-t butylisocyanide (99mTc-DEPIC) [13] have been used in GBPV acquisition [10, 11, 13]. As for these techniques, because of the rather weak binding of the radionuclide to the protein and the resulting fast extravascular diffusion [11], labeled RBC remain the radiopharmaceutical in routine practice [19]. Our work showed that 99mTc-IgG had a better washout rate from blood pools and background regions than 99mTc-RBC when used for cardiac blood-pool imaging [18]. Such an in-creased washout rate does not reduce effective tracer activ-ity and the target-to background ratios. Although we did not document the washout rate directly by obtaining sequential blood samples, the heart-to-background ratios of the two radiopharmaceuticals was an indicator for this finding.Our findings may indicate that 99mTc-IgG is a promising agent for GBPV having a stable biodistribution and provid-ing good image quality up to 3h post injection. Even on the delayed study, a good contrast between the LV and the sur-rounding organs was acquired, permitting a precise calcula-tion of the EF value. We were unable to find a similar study in the literature. Further studies with more cases are needed to confirm these findings.In conclusion, our results showed that the use of 99mTc-IgG in cardiac blood pool studies might be an alternative to 99mTc-RBC for the measurement of LV and EF function.  All authors declare that they have no conflicts of interestOriginal Technical NoteTable 1. The main characteristics and results of the two groups studiedParameter Phase 99mTc-RBC 99mTc-IgG P valueLV/Liverearly 1.71±0.48 2.02±0.29 0.26delayed 1.78±0.48 1.93±0.30 1.00LV/Spleenearly 1.79±1.18 2.07±0.85 0.33delayed 1.55±0.57 1.78±0.45 0.52LV/Lungearly 1.43±0.48 1.70±0.18 0.33delayed 1.34±0.48 2.00±1.11 0.20RV/Liverearly 2.43±0.50 2.63±0.58 0.74delayed 2.04±0.67 2.50±0.63 0.42RV/Spleenearly 2.40±1.31 2.69±1.15 0.52delayed 1.73±0.61 2.32±0.68 0.20RV/Lungearly 2.00±0.43 2.20±0.41 0.42delayed 1.68±0.80 2.51±1.24 0.26  Aorta/Liverearly 0.83±0.28 0.81±0.32 0.87delayed 0.88±0.30 0.83±0.31 0.87Aorta/Spleenearly 0.83±0.49 0.79±0.40 0.52delayed 0.82±0.42 0.73±0.19 0.87Aorta/Lungearly 0.67±0.16 0.67±0.22 0.87delayed 0.69±0.33 0.80±0.35 0.52Liver/Spleenearly 1.05±0.66 1.05±0.46 0.63delayed 0.93±0.40 0.95±0.32 0.87ROI, region of interest; LV, left ventricle; RV, right ventricle.Hellenic Journal of Nuclear Medicine January - April 2011www.nuclmed.gr  Bibliography  1. Tabatabaee A, Pourbehi MR, Moghaddam M et al. Comparsion of influence of enoxaparin with unfractioned heparin on acute myocardial infarction with ST-segment elevation. ISMJ 2010: 198-205.2. Zaret BL, Wackers FJ, Terrin ML et al. Value of radionuclide rest and exercise left ventricular ejection fraction in assessing sur-vival of patients after thrombolytic therapy for acute myocar-dial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study. The TIMI Study Group. J Am Coll Cardiol 1995; 26: 73-9.3. Nichols KJ, Van Tosh A, Wang Y et al. Validation of gated blood-pool SPECT regional left ventricular function measurements. J Nucl Med 2009; 50: 53-60.4. Picano E, Lattanzi F, Orlandini A et al. Stress echocardiography and the human factor: the importance of being expert. J Am Coll Cardiol 1991; 17: 666-9.5. Canbaz F, Basoglu T, Yilmaz O et al. Comparison of gated pla-nar 99mTc tetrofosmin scintigraphy with radionuclide ventricu-lography and echocardiography in the evaluation of left ven-tricular wall motion. Ann Nucl Med 2003; 17: 15-22.6. Nichols K, DePuey EG, Krasnow N et al. Reliability of enhanced gated SPECT in assessing wall motion of severely hypoper-fused myocardium: echocardiographic validation. J Nucl Car-diol 1998; 5: 387-94.7. Daou D. SPECT radionuclide angiography: it is time for a consensus statement. Eur J Nucl Med Mol Imaging 2007; 34: 1729-34.8. Rojas-Burke J. Health officials reacting to infection mishaps. J Nucl Med 1992; 33: 13N-4N, 27N.9. Goins B, Phillips WT, Klipper R. Blood-pool imaging using tech-netium-99m-labeled liposomes. J Nucl Med 1996; 37: 1374-9.Original Technical Note10. Hambye AS, Verbeke KA, Vandermeiren RP et al. Comparison of modified technetium-99m albumin and technetium-99m red blood cells for equilibrium ventriculography. J Nucl Med 1997; 38: 1521-8.11. Nishimura T, Hamada S, Hayashida K et al. Cardiac blood-pool scintigraphy using technetium-99m DTPA-HSA: comparison with in vivo technetium-99m RBC labeling. J Nucl Med 1989; 30: 1713-7.12. Kelbaek H, Bulow K, Aldershvile J et al. A new 99mTc-red blood cell labeling procedure for cardiac blood pool imaging: clinical results. Eur J Nucl Med 1989; 15: 333-5.13. de Klerk JM, van Rijk PP, van Dongen AJ et al. Can technetium 99m bisdiethylphosphinoethanebis-t butylisocyanide (99mTc-DEPIC) be used for routine radionuclide ventriculography? Eur J Nucl Med 1991; 18: 317-20.14. Hesse B, Lindhardt TB, Acampa W et al. EANM/ESC guidelines for radionuclide imaging of cardiac function. Eur J Nucl Med Mol Imaging 2008; 35: 851-85.15. Callahan RJ, Froelich JW, McKusick KA et al. A modified meth-od for the in vivo labeling of red blood cells with 99mTc: concise communication. J Nucl Med 1982; 23: 315-8.16. Griffiths GL, Goldenberg DM, Jones AL, Hansen HJ. Preparation of a pure 99mTc-F(ab’)2 radioimmunoconjugate by direct labe-ling methods. Nucl Med Biol 1994; 21: 649-55.17. Massardo T, Jaimovich R, Lavados H et al. Comparison of radio-nuclide ventriculography using SPECT and planar techniques in different cardiac conditions. Eur J Nucl Med Mol Imaging 2007; 34: 1735-46.18. Harel F, Finnerty V, Ngo Q et al. SPECT versus planar gated blood pool imaging for left ventricular evaluation. J Nucl Car-diol 2007; 14: 544-9.19. Srivastava SC, Straub RF. Blood cell labeling with 99mTc: progress and perspectives. Semin Nucl Med 1990; 20: 41-51.Prof.B.Kokkas                                 The summit of mt. Olympus from an airplane,Macedonia,Greece

Comparison of technetium-99m IgG with technetium-99m red blood cells labeling in cardiac blood-pool scintigraphy: A preliminary study

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Comparison of technetium-99m IgG with technetium-99m red blood cells labeling in cardiac blood-pool scintigraphy: A preliminary study

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