Influence of exercise on the distribution of technetium Tc 99m medronate following intra-articular injection in horses.

OBJECTIVE: To determine the effects of exercise on the distribution and pharmacokinetics of technetium Tc 99m medronate ((99m)Tc-MDP) following intra-articular (IA) injection in horses. ANIMALS: 5 horses. PROCEDURES: 1 antebrachiocarpal joint (ACJ)/horse was assigned to the exercised group (n = 5), and the contralateral ACJ was evaluated in the nonexercised group (5) after a minimum washout period of 7 days. Following IA injection of (99m)Tc-MDP (148 MBq), blood and scintigraphic images of the carpus were obtained at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 240, 360, 480, 600, 720, and 1,440 minutes. Plasma and scintigraphic radioactivity were determined over time, and pharmacokinetic parameters were generated via noncompartmental and compartmental analyses. Each horse was monitored via physical and lameness examination and ACJ synovial fluid analysis before injection and at days 1, 2, 3, and 7. RESULTS: Lameness was not observed. Mean ± SD synovial fluid WBC count increased at day 1 (exercised, 721 ± 234 cells/µL; nonexercised, 948 ± 223 cells/µL), but returned to baseline at days 3 and 7 Mean time to maximum plasma radioactivity was earlier in the exercised group (16.00 ± 2.35 minutes) than the nonexercised group (43.75 ± 3.64 minutes). Linear regression of the scintigraphic radioactivity-time curves revealed a greater negative slope in the exercised group within the first 25 minutes. There was no difference in absorption or elimination rate constants in a 2-compartment model. CONCLUSIONS AND CLINICAL RELEVANCE: IA injection of (99m)Tc-MDP was safe and effective for evaluating synovial solute distribution. Exercise significantly increased early transfer of (99m)Tc-MDP from the ACJ into plasma, although absorption and elimination rate constants were not affected. Exercise may affect synovial clearance and withdrawal times of medications administered IA.

A study to determine the dependence of 99mTc-MDP protein binding on plasma clearance and serum albumin concentration.

BACKGROUND: The measurement of protein binding is essential for accurate quantitative studies of skeletal kinetics using Tc-methylene diphosphonate (Tc-MDP). In this study, the dependence of Tc-MDP protein binding on total plasma clearance (Ktotal) and serum albumin concentration was investigated using data from two groups of patients. METHOD: The first group (study 1) consisted of 71 patients referred for a Tc-MDP bone scan examination. The second group (study 2) consisted of 100 subjects referred for a determination of glomerular filtration rate (GFR) and injected with 3 MBq Tc-MDP and 3 MBq Cr-EDTA. Free Tc-MDP was measured using ultrafiltration and the percentage of free Tc-MDP analysed for the effect of Ktotal and serum albumin concentration using multivariate regression analysis. RESULTS: When the percentage of free Tc-MDP was analysed for the effect of Ktotal and serum albumin, highly significant relationships were found at the 2, 3 and 4 h time points. Subjects with higher values of Ktotal or serum albumin concentration had a lower percentage of free Tc-MDP and the magnitude of the regression coefficients increased with time. CONCLUSION: Multivariate regression analysis confirmed that Ktotal and serum albumin were highly significant factors in determining the percentage of free Tc-MDP measured at the 2, 3 and 4 h time points.

Validation of a blood-sampling method for the measurement of 99mTc-methylene diphosphonate skeletal plasma clearance.

UNLABELLED: Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating (99m)Tc-MDP kinetics involves taking multiple blood samples and measuring total clearance (K(total)) from the area under the plasma curve (AUC) and deriving bone clearance (K(bone)) by subtracting glomerular filtration rate (GFR) from K(total). However, the accuracy of the AUC method is uncertain because of assumptions that the terminal exponential is reached by 2 h and that the rate constant k(4), representing the backflow of tracer from bone to plasma, is negligibly small. The aim of this study was to validate the accuracy of the AUC method by comparing K(bone) values obtained by that method with those obtained by gamma-camera imaging. METHODS: Seventy-one patients were injected with 600 MBq of (99m)Tc-MDP. For the first 22 patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after injection, whereas the remaining 49 were imaged at 15 min and at 1 and 3 h. Two-minute static images of the thighs were acquired immediately before each whole-body scan. Multiple blood samples were taken between 5 min and 4 h, and free (99m)Tc-MDP was measured using ultrafiltration. Two gamma-camera methods were used to evaluate K(bone): the Patlak plot method and the Brenner method, which is based on measuring soft-tissue uptake in the thighs. The soft-tissue data were also used to measure k(4). RESULTS: The soft-tissue data gave a k(4) value of 0.0003 min(-1) (95% confidence interval, 0-0.0008 min(-1)). The mean (+/-SD) (99m)Tc-MDP K(bone) was 56.0 +/- 32.4 mL x min(-1) with the AUC method, 49.5 +/- 32.1 mL x min(-1) with the Patlak method, and 42.8 +/- 32.0 mL x min(-1) with the Brenner method. Correcting the AUC values of K(total) by factors of 0.95 and 0.90 gave K(bone) values in agreement with the Patlak and Brenner methods, respectively. CONCLUSION: Values of k(4) are too small to affect values of K(bone) measured using the AUC method. Correcting K(total) by factors in the range of 0.90-0.95 corrects for the error in the terminal exponential and brings K(bone) values measured using the AUC method into agreement with the gamma-camera results.

Validation of ultrafiltration as a method of measuring free 99mTc-MDP.

UNLABELLED: Quantitative studies of the kinetics of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) in metastatic and metabolic bone disease require the measurement of free tracer in plasma to derive the input function. Several methods of measuring free (99m)Tc-MDP have been described including ultrafiltration, precipitation using trichloroacetic acid, and a direct in vivo measurement based on the assumption that free MDP is cleared through the kidneys by glomerular filtration. The aim of this study was to validate ultrafiltration as a convenient and accurate method of measuring the free fraction of (99m)Tc-MDP by comparing it with the glomerular filtration rate (GFR) method. A second aim was to measure the percentage of free (99m)Tc-MDP in a cross-section of patients using ultrafiltration to determine the interpatient variability and, therefore, whether individual measurements are required for bone kinetic studies. METHODS: In study 1, 10 volunteers (7 women, 3 men; mean age, 37 y; range, 26-55 y) were injected with 3 MBq (99m)Tc-MDP and 3 MBq (51)Cr-ethylenediaminetetraacetic acid, and multiple blood and urine samples were taken between 0 and 4 h. Plasma samples were spun in 5-, 10-, and 30-kDa filters and counted in a gamma-counter. In study 2, 51 randomly selected patients (26 women, 25 men; mean age, 66 y; range, 31-87 y) attending our department for a routine bone scan were injected with 600 MBq (99m)Tc-MDP, and 4 blood samples were taken between 0 and 4 h and spun in 10-kDa filters. RESULTS: In study 1, the mean percentages (+/-SD) of free (99m)Tc-MDP at 5 min and 4 h after injection measured using the 10-kDa filters were 83.1% +/- 3.4% and 44.0% +/- 10.0%. The mean ratios (+/-SEM) of the free (99m)Tc-MDP in ultrafiltrate compared with the GFR method for the 5-, 10-, and 30-kDa filters were 0.894 +/- 0.010, 0.943 +/- 0.009, and 0.987 +/- 0.010. In study 2, the mean percentages (+/-SD) of free (99m)Tc-MDP at 15 min and 4 h were 75.3% +/- 8.0% and 48.8% +/- 9.5%, with a precision error of 2.3%. The percentages of free MDP at 150 min and 4 h were significantly correlated with GFR but not with serum albumin. CONCLUSION: Ultrafiltration provides an accurate method of evaluating free (99m)Tc-MDP in plasma for bone kinetic studies. The results from both the healthy volunteers in study 1 and the patients in study 2 show that protein binding varied with time and showed significant differences between individuals that were partly dependent on GFR. It is thus necessary to measure individual protein binding values for bone kinetic studies.

A direct in vivo measurement of 99mTc-methylene diphosphonate protein binding.

Quantitative studies of the kinetics of 99mTc-methylene diphosphonate (99mTc-MDP) in metabolic and metastatic bone disease require the measurement of free tracer in plasma to derive the input function. We describe a simple method of determination of free 99mTc-MDP in vivo based on measurements of the ratio of the renal plasma clearances of total 99mTc-MDP and 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free 99mTc-MDP were made between 0 and 4 h after injection in 70 postmenopausal women enrolled in a study of the effect of hormone replacement therapy on the whole-skeleton plasma clearance of 99mTc-MDP (K(bone)). The glomerular filtration rate (GFR) was measured simultaneously from the plasma clearance of 51Cr-EDTA. The mean fractions (and SD) of free MDP measured were 0.757 (0.050), 0.663 (0.062), 0.550 (0.052) and 0.472 (0.053), respectively, at 17, 90, 150 and 210 min after injection. The results agreed closely with data using protein precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the biological half-life of free 99mTc-MDP in plasma was 92 min, compared with 540 min for bound MDP. Highly significant relationships were found between the fraction of free MDP measured in each patient at each of the four time points and the total plasma clearance of free 99mTc-MDP (K(total)=GFR+K(bone)), such that a larger value of K(total) was associated with a smaller fraction of free MDP. Multivariate regression analysis confirmed that this relationship held individually for both GFR and K(bone). A strong inverse relationship was found between K(total) and the plasma concentration of free 99mTc-MDP, but a much weaker relationship with the bound MDP concentration, a finding that is consistent with the slow re-equilibration of bound MDP in the circulation. The results confirm that the fraction of free 99mTc-MDP varies with time and shows significant differences between individuals, which are dependent on GFR and K(bone) amongst other factors.

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.

Radiopharmacokinetic data for 99mTc-ABP--a new radiopharmaceutical for bone scanning: comparison with 99mTc-MDP.

Technetium-99m-labeled alendronate is a new radiopharmaceutical for bone scanning developed under strict quality control at the INNSZ. The purpose of this work was to compare the radiopharmacokinetic data and the dosimetry of 99mTc-ABP and 99mTc-MDP in 10 volunteers, after it was tested in laboratory animals. 99mTc-ABP has shorter mean residence time (MRT) and t 1/2 beta; is less protein bound; has a higher renal clearance; smaller Vdss, and similar bone uptake at 1 and 2 h. 99mTc-ABP gives less radiation exposure to the patient with a 740 MBq dose, and the quality of the bone scan is excellent. 99mTc-ABP is a better radiopharmaceutical than 99mTc-MDP for bone scanning.

Binding of 99mTc(113Sn)-MDP to human serum albumin. The influence of various technetium, tin, and MDP concentrations.

The HSA-binding of 99mTc incubated as 99mTc(113Sn)-MDP depends in vitro on the presence of competing anions normally present in plasma and on the MDP and Tc concentration, but is independent of the Sn concentration. The HSA-binding of 113Sn depends on the MDP and Sn concentration; not on the Tc concentration. 99mTc(Sn)-MDP binds to HSA as a unit. The binding of 99mTc(Sn)-MDP to plasma proteins in vivo is much lower as calculated from in vitro experiments because of competition between 99mTc(Sn)-MDP and endogenous anions for the same binding-sites.