The evaluation of an isotope clearance technique in the dermis of pig skin: A correlation of functional and morphological parameters

A dermal isotope clearance technique has been assessed in pig skin. Following an intradermal injection, the tracer (^99mTc) is cleared from this site by both a fast and a slow exponent (biexponential clearance). From a comparison of age-related changes in the clearance parameters with the thickness and vascular density of the dermis, it is proposed that the two clearance exponents are related to two distinct vascular networks within the dermis: the fast exponent results from clearance by the vessels of the superficial papillary dermis while the slow exponent denotes clearance by the vessels of the reticular dermis. This evidence is further supported by changing the depth of injection; clearance rates are not affected by injection depth, but after a “deep” injection a greater proportion of isotope is removed by the slow exponent (clearance from the reticular dermis). It is concluded that the clearance of ^99mTc pertechnetate not only measures the clearance capacity of the blood flow but also relates to the number of vessels present per unit volume of the tissue under investigation. These findings may lead to a clearer understanding of isotope clearance parameters in other normal tissues.     

Participation of the arterial and portal drainage in the calculation of total hepatic blood flow in guinea pigs

Experiments were performed on partly isolated livers of guinea pigs. The hepatic outflow (HOF) was measured by an electromagnetic flowmeter placed on the inferior vena cava. Nutritive hepatic blood flow (HBF) was measured with ¹³³Xe bolus technique with the tracer injected into the portal vein or hepatic artery. Under unchanged perfusion conditions, three exponents could be demonstrated irrespective of the site of injection. Two of them observed during the first 5 min represent the intrahepatic, the third (slowest one) the extrahepatic blood flow. Occlusion of either the portal vein or the hepatic artery results in a monoexponential decrease during the first 5 min. Calculation of the HBF was based on an equation including both components of the washout curves obtained after arterial and portal application. The calculated HBF was equal to the value of the directly measured total outflow but overestimated HBF_f calculated from the first exponent of the washout curve obtained after intraportal tracer application.     

Measurement of the lymphatic clearance of the human skin using a fluorescent tracer

The lymphatic clearance of the human skin at the instep of the foot was measured in 20 healthy volunteers (mean age +/- SD 33.8 +/- 10.5 years). Ten microliters of fluorescein isothiocyanate-dextran 150,000 were injected intradermally and the fluorescent light intensity of the deposit was measured 10 min and 24 h after injection by window densitometry. Fluorescent light intensity decreased by 31.2 +/- 13.5 arbitrary units (p < 0.0001) or by a factor of 4.1 +/- 3.9. Reproducibility was tested 2-6 weeks later in 7 subjects and an intraclass reliability of 0.76 was found. These are the first measurements of the lymphatic clearance of the human skin using a fluorescent tracer. The method is easier and safer than the isotope clearance technique and small areas of the human skin can be investigated. The data found form a basis with which to compare measurements made in patients with different forms of edema.     

Quantification of pulmonary blood flow by a radioisotope technique: validation in normal dogs, and in dogs with aortopulmonary shunts

Pulmonary blood flow was measured in dogs by injecting ^99mTc human serum albumin into the main pulmonary artery and recording the isotope dilution curve obtained from external counting over the lungs. The area under the curve was calibrated by comparing the blood concentration of isotope with the recording from the external counters when the isotope had reached equilibrium in the blood. Forty simultaneous dye dilution and isotope dilution curves were obtained. The cardiac ouput was deliberately changed by drugs to obtain a range of values and, in some experiments, dogs with surgically created aortopulmonary shunts were used. A significant correlation was found between the values for pulmonary blood flow obtained by the dye and isotope dilution methods (r = 0.96), there was no systematic discrepancy between the two methods, and both were reproducible. The isotope dilution curves were easier to analyze than the dye dilution curves in the presence of left-to-right shunts. It is suggested that this method may simplify the measurement of pulmonary blood flow in infants and children with congenital heart disease since it is relatively undisturbing, less invasive than other methods, and uses an acceptably low radiation dose.     

Distribution of the collateral blood flow at the lateral border of the ischemic myocardium after acute coronary occlusion in the pig and the dog

Summary Residual blood flow in pigs (n=8) and dogs (n=11) was measured by tracer microspheres (⁵⁸Sr) 1 hour after occlusion of the left anterior descending coronary artery (LAD). Collateral blood flow was distinguished from overlap flow, defined as the blood flow of non-ischemic myocardium interdigitating into the ischemic area, by direct LAD injection of isotope-labelled microspheres (¹²⁵I) prior to ligation. In the center of the acutely ischemic pig myocardium the residual blood flow, i.e., the myocardial perfusion remaining after LAD occlusion, was 0.01±0.01 ml/min/g subendocardially and 0.02±0.01 ml/min/g subepicardially, as estimated with⁸⁵Sr-labelled microspheres. These values were significantly lower than the corresponding values for the dog, 0.13±0.05 ml/min/kg (p<0.05) subendocardially and 0.28±0.08 ml/min/g (p<0.01) subepicardially. In the lateral aspects of the ischemic area, calculations of overlap flow were made with the aid of the distribution of the microspheres injected into the LAD. Values of the residual blood flow were normalized and nonischemic myocardial perfusion was set to 100 units. In subepicardial layers of the myocardium with calculated overlap flows corresponding to 20, 50 or 80 units, respectively, the residual blood flow (overlap flow + collateral flow) actually measured in the pig was 31±4 55±4 and 75±7 units and in the dog 65±6, 79±5 and 91±2 units. The values for the dog were significantly different from the respective value for the pig (p<0.01). In the subendocardial layers the difference between the two species regarding residual blood flow was similar, although the difference was statistically significant only for myocardium with a calculated overlap flow of 80 units. When the calculated overlap flow was subtracted from the measured residual blood flow, the collateral blood flow was found to be extensive in the dog and virtually absent in the pig.When, in the dog, the collateral blood flow across the lateral border of the ischemic area was related to the amount of myocardium it supplies, it was found to be homogeneously distributed. Thus neither subendocardially nor subepicardially could a gradient of collateral blood flow be detected. It is concluded that in the pig the collateral blood flow is almost nil throughout the acutely ischemic myocardium, both in subendocardial and subepicardial layers. In contrast, the dog has an extensive collateral flow. No lateral gradient of this collateral blood flow could, however, be detected.     

Analysis of left ventricular function from gated first-pass and multiple gated equilibrium acquisitions

^99mTechnetium-sestamibi is a new myocardial perfusion imaging agent that offers significant physical advantages over²⁰¹thallium for myocardial perfusion imaging. One of these advantages is that it can be used in the assessment of ventricular function by means of first-pass radionuclide angiography (FPRNA), acquired during the injection of the tracer. In this study we compared gated list mode first-pass acquisition with^99mTc-sestamibi (FP-MIBI) to multiple gated equilibrium radionuclide ventriculography (MUGA) with^99mTc-labelled red blood cells for the determination of global left ventricular ejection fraction (LVEF). The study population consisted of 20 patients (mean age 54 years) who were submitted to stress-rest perfusion imaging. Resting FPRNA was performed using^99mTc-sestamibi and the reference data were acquired within a week with the MUGA technique. A linear correlation between FP LVEF and MUG A LVEF gave an r=0.974 (p<0.01). Diastolic and systolic timing and velocity parameters had lower correlations between these two methods. We conclude thatglobal LVEF can be precisely measured with^99mTc-sestamibi when compared to usually employed MUGA technique with^99mTc-labelled red blood cells.     

Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses.

BACKGROUND: Technetium 99m N-DBODC5 is a new myocardial perfusion tracer shown to exhibit high heart uptake and rapid liver clearance in normal rats. The objectives of this canine study were (1) to compare the organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 with Tc-99m sestamibi over a period of 3 hours in a more clinically relevant large animal species and (2) to compare the myocardial uptake of Tc-99m N-DBODC5 with thallium 201 when co-injected during vasodilator stress in dogs with coronary stenoses. METHODS AND RESULTS: At peak adenosine-induced hyperemia, 10 dogs with critical left anterior descending artery stenoses received either Tc-99m N-DBODC5 (n = 6) or Tc-99m sestamibi (n = 4) and microspheres, followed by serial imaging and blood sampling over a period of 3 hours. Another 14 dogs with either critical (n = 7) or mild (n = 7) left anterior descending artery stenoses underwent simultaneous injection of Tc-99m N-DBODC5, Tl-201, and microspheres during peak vasodilator stress. Like sestamibi, Tc-99m N-DBODC5 showed good myocardial uptake with slow washout and minimal redistribution over a period of 3 hours (P = not significant); however, Tc-99m N-DBODC5 cleared more rapidly from the liver (heart-lung ratio at 30 minutes, 0.92+/-0.11 versus 0.51 +/- 0.05; P < .05). When injected during hyperemic flow, the myocardial extraction plateau for Tc-99m N-DBODC5 was lower than that for Tl-201 and was intermediate between Tc-99m sestamibi and Tc-99m tetrofosmin. CONCLUSIONS: Excellent organ biodistribution and myocardial uptake and clearance kinetic properties, combined with rapid liver clearance and a favorable flow-extraction relationship, make Tc-99m N-DBODC5 a very promising new myocardial perfusion imaging agent.     

Measurement of blood flow by thermodilution

In thermodilution a known change in heat content of the blood is induced at one point of the circulation and the resultant change in temperature detected at a point downstream. When cardiac output is measured, a bolus of cool liquid is injected into the upper right atrium and the temperature change detected in the pulmonary artery. When flow in single blood vessels is measured, the distance between the site of injection and the site of detection is small; therefore, mixing must be attained by the kinetic energy of the injectate. The continuous constant rate injection technique is most suitable for measurement of venous flow. Since the blood flow in arteries can be markedly and unpredictably altered by the injection or the injectate, this technique is not suitable to measure flow in arteries. Measurement of venous flow by the bolus injection technique is tedious and time-consuming because of the complex formula. Minimal recirculation, simple and accurate calibration, intravascular detection of temperature and simple equipment are the advantages of the thermodilution technique.     

99mTechnetium scintiphotography in arthritis I. technic and interpretation

A technic for visualization of inflamed joints using intravenously injected technetium-99m as pertechnetate and an Anger (scintillation) camera for detection will be described. Contrast between inflamed and normal tissue was usually greatest in the first few minutes after isotope injection, presumably, at the time of maximal difference in concentration of ^99mTc between blood and extravascular tissue. Inflamed joints with moderate to large effusions were often visualized best 1–2 hr after injection. The extensive binding of pertechnetate by plasma and joint fluid proteins found in equilibrium dialysis experiments was evoked as an explanation of this phenomenon.     

Early changes in capillary flow and transport following missile wounds

The local hemodynamic response to missile wounds in soft tissue has been studied on 31 mongrel dogs with a double isotope clearance technique using sodium iodide (Na¹³¹I) and xenon (¹³³Xe). Three different impact velocities with a small spherical projectile were used to vary the amount of energy absorbed by the tissues. The isotope was injected at a constant depth but at varying distances from the wound site. The flow responses (i.e., xenon clearance) were quite variable, but there was a tendency toward greater responses between 35 and 45 mm from the wound channel after high-velocity missile wounds. The same tendency was seen more clearly for iodide clearance values. The size of the damage by missiles hitting with the three velocities used is discussed. Because of irregularities in the volume of tissue absorbing the energy, variations in individual animals could be expected. However, the flow pattern recorded with the isotope clearance technique coincides in both time and localization with the hemodynamic and angiographic findings after wounds caused in a similar way and reported previously.     

Comparison of technetium-99m sestamibi and thallium-201 retention characteristics in canine myocardium.

OBJECTIVES. The aim of this study was to compare the myocardial retention of technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood flow at different time points after tracer injection. BACKGROUND. Technetium-99m sestamibi has been proposed as a new perfusion tracer with better physical characteristics than those of thallium-201 for scintigraphic imaging. However, no studies have simultaneously compared the ability of both tracers to assess myocardial blood flow during pharmacologic vasodilation. METHODS. The myocardial retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of blood flow induced by regional coronary occlusion and dipyridamole infusion in an open chest dog model. Myocardial retention of both tracers was determined by in vitro tissue counting at 2, 5, and 20 min after tracer injection and was correlated with microsphere-determined blood flow. RESULTS: Thallium-201 demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2 min after tracer injection, there was an almost linear relation between the retention of both tracers and myocardial blood flow over a wide flow range. However, this relation was not maintained over time. At 20 min after injection, the retention of both tracers underestimated myocardial blood flow at higher flow rates. At 2, 5 and 20 min after injection, increments of relative tracer retention between the different levels of flow were always greater for thallium-201 than for Tc-99m sestamibi. CONCLUSIONS. Thallium-201 displays more suitable physiologic characteristics as a flow tracer and may allow better differentiation of myocardial regions with different levels of coronary flow reserve. For both tracers, early cardiac imaging may minimize underestimation of blood flow at higher flow rates.     

The relationship between myocardial retention of technetium-99m teboroxime and myocardial blood flow.

OBJECTIVES. The aim of this study was to define the temporal changes in the relationship between technetium-99m teboroxime tissue retention and myocardial blood flow in a canine model. BACKGROUND. Technetium-99m teboroxime is a new neutral lipophilic myocardial perfusion agent. It is known to be highly extracted by the myocardium but to have a rapid clearance rate. METHODS. A wide range of myocardial blood flow was induced in each experiment by regional coronary occlusion and dipyridamole infusion. Myocardial retention of technetium-99m teboroxime was determined by in vitro tissue counting at 1, 2 or 5 min after injection of the tracer. Tracer retention was correlated with microsphere-determined blood flow and the data were fitted to nonlinear functions. RESULTS. Correlation coefficients for these functions were 0.92, 0.95 and 0.95 at 1, 2, and 5 min, respectively. At 1 min after injection, the relationship of technetium-99m teboroxime retention to blood flow was linear over a wide flow range, becoming nonlinear at flow rates greater than 4.5 ml/min per g. After 5 min the retention-flow relationship was linear only to 2.5 ml/min per g, above which little change in retention was noted. Normalized myocardial retention, expressed as a percent of the retention at 1 ml/min per g, was also calculated. At flow rates of 1, 2, 3, 4 and 5 ml/min per g, normalized retention was 100, 169, 228, 277 and 317% at 1 min and 100, 171, 217, 239 and 237% at 5 min after injection. CONCLUSIONS. At 1 min after injection, the relationship of technetium-99m teboroxime myocardial retention to blood flow is well maintained over a wide range of flow. However, after only 5 min, tracer retention underestimates flow changes at moderate and high flow rates. Thus, rapid acquisition protocols are necessary to fully exploit the potential of this promising new tracer in the evaluation of myocardial perfusion.     

Inhalation and Perfusion Lung Scans in Bronchial Asthma

Inhalation and perfusion lung scans were performed in 15 patients with bronchial asthma, during an exacerbation and during a relatively symptom-free phase in each patient. The inhalation scans were obtained using an aerosol containing a Tc^99m-iron complex, the perfusion scans with intravenously injected I¹³¹ macro-aggregated albumin. The pulmonary distribution of both inhaled and injected material was uneven in all 15 patients during exacerbations of asthma. The distribution of both inhaled and injected material became more even as the patients recovered. The limitations of an inhaled radio-active aerosol as an indicator of uneven distribution of ventilation were explored. In particular, it was found that aerosol was selectively deposited on sputum lying proximally in the bronchial tree. In five patients during an exacerbation of asthma, the distribution of isotope in the perfusion scan was very similar to the distribution of isotope in the inhalation scan. This indicates fairly good matching of blood flow distribution with abnormal ventilation distribution on a topographical basis in such patients.     

Measurement of microvascular permeability to small solutes in man: limitations of the technique

STUDY OBJECTIVE--The aim was to evaluate the limitation on the measurement of the clearance rate of a small solute, 99mTc DTPA, from intravascular to extravascular spaces imposed by diffusion of the solute back into blood during the period of measurement. DESIGN--The technique for measuring clearance also generates the regional plasma volume from which the solute is cleared. Back diffusion would result in an overestimation of this plasma volume. By applying the same technique to 99mTc labelled human serum albumin, which is not cleared over the period of measurement, a separate estimate of plasma volume can be made. SUBJECTS--The subjects were eight patients undergoing routine 99mTc DTPA renography for suspected outflow obstruction. MEASUREMENTS AND RESULTS--The ratio of plasma volumes based respectively on 99mTc DTPA and human serum albumin in a region of interest below the kidney was 1.04 (SD 0.09). The technique requires a region of interest over the cardiac blood pool from which the blood level of 99mTc DTPA is continuously monitored. When a correction was made for extravascular 99mTc DTPA in this cardiac region of interest, the ratio was unchanged: 0.97 (0.12). CONCLUSION--The technique is capable of measuring the clearance of 99mTc DTPA although, because of its small molecular size, the transfer rate is blood flow dependent, ie, its PS product is greater than its clearance.     

Venous delay, a major source of error in isotopic cardiac output determination.

The high correlation reported for cardiac output determinations by ^99mTc-HSA has not held for other unselected series. To investigate possible causes, cardiac output was determined simultaneously by two indicators: ^99mTc-HSA and indocyanine green both injected by rapid flush technique, the ^99mTc via antecubital vein and the dye (DD) via superior vena cava. Precordial counting rates were obtained by scintillation camera and dilution curves were derived by computer program from selected areas in right (RV) and left ventricles (LV). Thirty consecutive studies showed significant (p < 0.001) correlation (r = 0.81) between ^99mTc and DD output but a determination index of only 66 per cent. Varying degrees of persistence of counting rate were noted in the subclavian region in the absence of demonstrable venous obstruction. In seven studies (Group I) there was no isotope hang-up in the subclavian region; in 17 (Group II), counts in the subclavian region persisted only through RV visualization, and in six studies (Group III) counts persisted even when radioactivity was at its peak concentration over LV. Correlation coefficients (^99mTc output with DD output) varied inversely with delay; r was 0.90 for Group I and Group II, and 0.64 for Group III (determination indices 81 per cent, 81 per cent, and 41 per cent, respectively).Results suggest that unexpected delay in arrival of radioactive bolus into the heart results in erratic distortion of cardiac output values. Unless monitored, delay often remains unsuspected; in a consecutive series of 63 ^99mTc studies severe delay occurred in 16 per cent.The reason for the delay is not clear. It did not seem related to the speed of circulation, to the presence of venous obstruction, or to anatomical variations. It could not be related to the speed of injection or to the physical characteristics of the injectate.     

Carboplatin dosing based on measurement of renal function — experience at the Peter MacCallum Cancer Institute

Background: Carboplatin is used in treating many types of cancer. Because renal excretion is the major variable determining the pharmacokinetics of this drug, a dosing formula based on glomerular filtration rate (GFR) has been proposed and is being increasingly used in carboplatin dosing. This method of dosing is critically dependent on accurate measurement of GFR. Aims: To report the experience at a single major oncology centre of carboplatin dosing based on GFR, and comparisons of different methods of measuring renal function for use in this dosing method. Methods: An initial group of patients (n=24) was studied where GFR was measured by Cr⁵¹EDTA clearance and compared to Tc^99mDTPA clearance, measured 24 hour urine creatinine clearance and the Cockcroft and Gault formula. The carboplatin area under the plasma concentration versus time curve (AUC) was calculated using total platinum measured in a single blood sample assayed by flameless atomic absorption spectrophotometry. A subsequent patient group (n=16) was then studied using Tc^99mDTPA clearance to measure GFR. Results: Carboplatin dosing using Cr⁵¹EDTA clearance to measure GFR was accurate (<25% difference between planned and measured AUC) in 87% of samples. Estimation of renal function using the Cockcroft and Gault formula correlated with Cr⁵¹EDTA clearance only in patients with GFR <100 mL/minute. The measured 24 hour urine creatinine clearance did not correlate with Cr⁵¹EDTA clearance. Using Tc^99mDTPA clearance to measure GFR, carboplatin dosing was accurate in 81% of samples. Across a GFR range of 42–239 mL/minute, the Cr⁵¹EDTA and Tc^99mDTPA clearances were closely correlated (r=0.98, slope of regression line=1.02). Conclusions: Carboplatin dosing using a pharmacological formula based on GFR produces accurate targeting of the carboplatin AUC. Tc^99mDTPA clearance can be used to measure GFR instead of Cr⁵¹EDTA clearance, which is both more convenient and has potential cost savings. Estimates of renal function using the Cockcroft and Gault formula or measured 24 hour creatinine clearance are insufficiently accurate to use for carboplatin dosing.     

Non-invasive measurement of renal blood flow with 99mTc DTPA: comparison with radiolabelled microspheres

This technique for non-invasive measurement of renal blood flow is based on the principle of fractionation of cardiac output, and applicable with any recirculating gamma activity tracer. It effectively determines the count rate that would be recorded over the kidney if the tracer behaved like radiolabelled microspheres and was completely trapped in the kidney on first pass. After correction for kidney depth, the estimated first pass activity plateau, expressed as a fraction of the injected dose, is equal to the kidney's fraction of cardiac output. The principle of the technique was validated by comparison with renal blood flow based on radiolabelled microspheres. Nine separate comparisons were made in two anaesthetised dogs. A known dose of 99mTc radiolabelled microspheres (particle size 23-45 microns) was injected into the left ventricle and the count rate over each kidney recorded. A known dose of 99mTc diethylenetriaminepenta acetic acid (DTPA) was then given as an intravenous bolus and the data recorded dynamically with a gamma camera online to a computer. After subtraction of the stable signal arising from the preceding radiolabelled microspheres, the theoretical first pass activity plateau from the DTPA that would have been recorded if the DTPA, after reaching the systemic circulation, had behaved like radiolabelled microspheres and become completely trapped in the renal vascular bed, was estimated. Using doses based on syringe counts before and after injection the ratio of renal blood flow values given by the two techniques (DTPA:RLMS) was 1.14 (SD 0.22) for the left kidney and 1.1(0.17) for the right. Using doses based on whole body counts, corresponding ratios were 1.05(0.11) and 1.02(0.13).(ABSTRACT TRUNCATED AT 250 WORDS)     

A scintiphotographic method for measuring left ventricular ejection fraction in man without cardiac catheterization

A radioactive tracer method for the measurement of left ventricular ejection fraction in man without cardiac catheterization is described. The tracer (^99mtechnetium-labeled albumin) is injected intravenously. Images of the heart at end-systole and end-diastole are obtained using a scintillation camera and an electronic gate triggered by the patient's electrocardiogram. Each image is composed of 300,000 counts, representing a summation of 200 to 400 heartbeats at end-systole and end-diastole. An outline of the left ventricular free wall is drawn from each gated image. The position of the aortic and mitral valve planes is determined using a radionuclide angiogram obtained at the time of tracer injection. Left ventricular ejection fraction is calculated from the area and length of the long axis of the ventricular outline at end-systole and end-diastole. Determinations of ejection fraction in 20 patients using this tracer method were correlated with measurements obtained by contrast cineangiography with the following results: ejection fraction r = +0.92, P < 0.001; end-diastolic volume r = −0.76, P < 0.001; and end-systolic volume r = −0.75, P < 0.001.     

Experimental study of new diagnostic system for coronary artery disease using coronary transit index

OBJECTIVES: Noninvasive cardiac imaging techniques have had an increasing role in the diagnosis of coronary artery disease. However, these techniques are not widely available as a tool in the office setting. The purpose of this study was to provide an accurate assessment of coronary artery disease for screening purposes using Coronary Transit Index (CTI) assessment with small, high-resolution gamma cameras. METHODS: Total coronary blood flow was measured with ultrasonic flow probes placed around the left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery in a total of 33 conditions in 5 healthy mongrel dogs. The coronary blood flow was reduced stepwise with vascular occluders placed around the coronary arteries. The procedure for obtaining CTI included 4 parts: 1) The animal was injected intravenously with a bolus of a radioactive tracer (2.5-5.0 mCi of (99m)Tc-DTPA); 2) Dedicated gamma sensors monitored the passage of the injected bolus; 3) Time-activity curves were measured at the left ventricle with and without its wall; 4) The ratio of the washout rates of the 2 curves determined the CTI. RESULTS: Coronary Transit Index was successfully obtained from the left ventricle. The coronary blood flows measured by flow probes were well correlated with the regional myocardial blood flow. The percentage of the baseline value of the total coronary blood flow had the highest correlation (R=0.807, p<0.0001) with the Coronary Transit Index. CONCLUSIONS: These data indicated that a new diagnostic system using CTI successfully identified reduced coronary blood flow.     

Radioimmunolocalization of human pancreatic carcinoma xenograft by99mTc-labeled YPC3 monoclonal antibody

Monoclonal antibodies specific to tumor cells may be a useful tool for the diagnosis and treatment of carcinomas. In this study, YPC3 mAb, a specific monoclonal antibody against the human pancreatic carcinoma cell line Capan-2, was labeled directly with^99mTc after being pretreated with 2-mercaptoethanol. The radiolabeling efficiency was found to be high (88%–95%) and the immunoreactivity retained, as assessed by immunohistochemistry and enzyme-linked immunosorbent assay. The biodistribution of^99mTc-YPC3 mAb in nude mice bearing Capan-2 pancreatic carcinoma xenografts was studied and compared with that of labeled mouse immunoglobulin G(^99mTc-nmIgG). The xenograft uptake values per gram of tissue 6 h and 24 h after injection of^99mTc-YPC3 mAb were found to be, respectively, 4.72% ID/g and 8.42%ID/g, and the tumor/blood ratios 1.16 and 2.24. At 6 h and 24 h after injection of^99mTc-nmIgG, the uptakes were 2.89%ID/g and 1.80%ID/g, and the tumor/blood ratios 0.84 and 1.02 respectively. External imaging by single-proton emission computed tomography, 24 h after injection of^99mTc-YPC3 mAb, revealed clear scintigraphic visualization of Capan-2 xenografts, whereas injection of^99mTc-nmIgG did not. This study suggests that^99mTc labeling of monoclonal antibody YPC3 might be of practical value in localization diagnosis of human pancreatic carcinoma.Abbreviations nmIgG normal mouse immunoglobulin G - T/NT radioactive ratio of tumor/non-tumor tissue - %ID/g percentage of injected dose per gram of tissue