Absolute 24 h quantification of 99Tcm-DMSA uptake in patients with severely reduced kidney function: a comparison with 51Cr-EDTA clearance.

The aim of this study was to determine whether absolute 24 h DMSA uptake measurements (%DMSA) correlate well with 51Cr-EDTA clearance measurements in patients with severely reduced kidney function (SRKF). Between 1990 and 1997, 55 of 482 patients who underwent EDTA clearance measurements also underwent %DMSA within 1 week. Of these, 31 were women and 24 were men (mean age 60 years; range 19-77 years). EDTA clearance was determined using the slope-intercept method. Absolute depth- and background-corrected %DMSA were determined 24 h following the injection of 185 MBq per 1.73 m2 freshly prepared 99Tcm-DMSA. All patients had EDTA clearance < or = 60 ml.min-1. Eighteen patients (group A: 9 men and 9 women, mean age 55.8 years, range 28-73 years) had EDTA clearance > 20 ml.min-1 (mean +/- S.D. = 30.9 +/- 13.8 ml.min-1), whereas 37 patients (group B: 22 women and 15 men, mean age 62.0 years, range 19-77 years) had EDTA clearance < 20 ml.min-1 (mean +/- S.D. = 10.2 +/- 6.6 ml.min-1). EDTA clearance correlated well with %DMSA for the patients as a whole and for group A (r = 0.87, P = 0.73; r = 0.79, P = 0.0001 respectively). The regression equation suggests that %DMSA is not a marker of early renal dysfunction. In group B, the r-value (r = 0.48, P = 0.004) suggests that %DMSA is reliable as a marker of severe renal dysfunction to the extent that it provides rough information. In conclusion, %DMSA may not be used as a marker of early renal impairment. Additionally, in patients with severely reduced kidney function (EDTA clearance < 20 ml.min-1), it only provides a rough estimate.

Urinary excretion of tubular proteins and the technetium-99m dimercaptosuccinic acid (DMSA) absolute renal uptake in partial ureteral obstruction in rats: a functional evaluation of hydronephrotic kidneys.

The aim of this longitudinal study was to evaluate tubular proteinuria in rats with unilateral (UPO) and bilateral (BPO) partial ureteral obstruction with the dimercaptosuccinic acid (DMSA) scan as the gold standard for measuring renal tubular damage. We studied 70 female Wistar rats: 28 animals with UPO, 28 animals with BPO, 7 sham-operated animals, and 7 controls. All animals with obstructed ureters showed renal dilatation on the diethylenetriaminepentaacetic acid DTPA images 1 and 5 weeks postoperatively. One week following UPO and BPO, tubular proteinuria and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity increased (P < 0.01) and the absolute DMSA uptake decreased (P < 0.01). Persistently (week 6) high tubular proteinuria was found in 29% of the animals and was related to severe damage on the DMSA scan (P < 0.01) and to albuminuria (P < 0.05). Renal tubular damage was demonstrated by measuring renal enzymes, tubular proteins, and DMSA uptake after UPO and BPO. Persistent elevated tubular proteinuria was related to severely damaged kidneys.

Relationship of decreased chemotaxis of technetium-99m-HMPAO-labeled lymphocytes to apoptosis.

UNLABELLED: The purpose of this study was to evaluate chemotaxis and its relationship to apoptosis in 99mTc-HMPAO-labeled lymphocytes. METHODS: Peripheral lymphocytes, obtained from 12 healthy volunteers using lymphoprep, were divided in three equal fractions. One fraction was used as the control, one was labeled with cold HMPAO and one was labeled with 1.5 mCi (55.5 Mbq) 99mTc-HMPAO. Chemotaxis of T-lymphocytes was measured by the Boyden microchamber technique (BMA) (n = 8) using human monocyte chemotactic protein-3 (MCP-3) as chemoattractans. A chemotactic index was calculated as the number of HMPAO and 99mTc-HMPAO-labeled cells that migrated towards the MCP-3 solution, divided by the number of nonlabeled migrated lymphocytes. Apoptosis evaluation (n = 10) of unlabeled, HMPAO-labeled and 99mTc-HMPAO-labeled cells was performed using flowcytometry (FCM) forward light scatter analysis, 900 light scatter analysis, fluorescein-isothiocyanate (FITC)-labeled Annexin V and dye exclusion of propidium iodide. RESULTS: Chemotaxis of 99mTc-HMPAO-labeled T-lymphocytes was found to be reduced by approximately 31% (migration index of 0.69) (p = 0.01) as compared to both unlabeled and HMPAO-labeled lymphocytes, both the latter showing no difference in migration index. Whereas the mean percentages apoptotic lymphocytes in the unlabeled, 18.5%, and HMPAO-labeled fraction, 16.6%, were more or less comparable (p = 0.1), the mean percentage apoptotic cells in the 99mTc-HMPAO-labeled fraction was 51.8%, yielding a difference of 33.3% between 99mTc-HMPAO-labeled and unlabeled cells (p = 0.003). The procentual concordance between apoptotic cells (33.3%) and chemotactic impaired cells (31%) in the 99mTc-HMPAO-labeled fraction may be explained by the formation of a rigid cytoskeleton early in the apoptotic process that may theoretically limit chemotaxis. CONCLUSION: Using the BMA, chemotaxis of 99mTc-HMPAO-labeled lymphocytes was found to be reduced by approximately 31%. Furthermore, the percentage apoptotic lymphocytes induced by irradiation after labeling with 99mTc-HMPAO concurs well with the percentage of chemotaxis impaired cells.

Differential renal function measured by 99Tcm-DTPA and 99Tcm-DMSA in a complete unilateral renal obstruction rat model.

We performed a prospective study to determine whether 99Tcm-DTPA differential renal function (DRF) in the case of acute obstruction in a unipapillary kidney rat model shows a similar pattern of results as 99Tcm-DMSA in a multipapillary kidney model, and to exclude recirculation or a block of tubular transport of DMSA which might explain the discrepancy reported by Kelleher et al. In 15 male and 4 female Wistar rats (weight 300-350 g), 99Tcm-DMSA renal uptake was measured 24 h before complete obstruction of the right ureter, which served as reference values. Twenty-four hours after obstruction, 99Tcm-DTPA (18.5 MBq) renography and 99Tcm-DMSA (111 MBq) non-depth-corrected renal uptake measurements were performed in the 15 male rats; in the 4 female rats, 740 MBq of 99Tcm-DMSA were injected and absolute, non-depth-corrected renal uptake measured at 24, 48 and 72 h. 99Tcm-DMSA DRF of the right kidney ranged from 48 to 55% (mu: 51%; sigma: 2%) before obstruction and from 14 to 35% (mu: 24%; sigma: 6%) after obstruction, whereas 99Tcm-DTPA DRF ranged from 16 to 30% (mu: 25%; sigma: 4%). No significant differences were found between DRF measured by 99Tcm-DMSA and 99Tcm-DTPA (P = 0.18), or between DRF of the obstructed kidney as measured by 99Tcm-DMSA at 24, 48 and 72 h (P > 0.2). Hypothetically, the discrepancy between our findings and those of Kelleher et al. may be due to intratubular pressure. In conclusion, the present findings and those of Kelleher et al. suggest the differences in DRF following complete unilateral renal obstruction, as determined by DTPA and DMSA, are probably species-specific. Furthermore, recirculation and block of tubular transport are unlikely to contribute significantly to differences in DRF as measured by the two radiopharmaceuticals.

Lymphocyte labeling with technetium-99m-HMPAO: a radiotoxicity study using the micronucleus assay.

The cytogenetic radiation damage to lymphocytes after in-vitro labeling of mixed leukocytes and isolated lymphocytes with 99mTc-hexamethylpropyleneamine oxime (HMPAO) was evaluated using the cytokinesis-blocked micronucleus assay. A direct assessment of the radiation damage to the lymphocytes after a labeling procedure of leukocytes separated from 46 ml blood with 740 MBq of 99mTc-HMPAO was not possible due to an almost complete impairment of the proliferative capacity. By starting with isolated lymphocytes, the number of micronuclei was studied versus the intracellular activity concentration in the range 0-3 MBq/10(7) lymphocytes for three donors. A comparison of these results with the dose response of the micronucleus incidence in lymphocytes after in-vitro irradiation with x-rays allowed an individual assessment of the x-ray dose, inducing the equivalent amount of clastogenic damage as the intracellular activity after 99mTc-HMPAO labeling. Based on an extrapolation of these data, the radiation damage of the lymphocytes due to self-irradiation in a labeling procedure of leukocytes with 740 MBq of 99mTc-HMPAO was estimated to be equivalent to 26 Gy of x-rays. Due to the observed almost complete inhibition of the proliferative capacity at this high dose level, the increased risk for a lymphoid malignancy after administration of isolated lymphocytes or mixed leukocytes labeled with 99mTc-HMPAO activities sufficient for scintigraphy can be regarded as small.

Monitoring of prostate-specific antigen during external beam radiotherapy for carcinoma of the prostate.

In 35 patients with histologically confirmed carcinoma of the prostate confined to the pelvis, the value of prostate-specific antigen (PSA) was evaluated during external beam radiotherapy to the prostate and draining pelvic lymph nodes. In eleven patients initial prostate-specific antigen levels were more than 10 ng/ml and in twelve patients between 4 and 10 ng/ml. In the remaining twelve, initial prostate-specific antigen levels were less than 4 ng/ml. In the course of radiotherapy we could see a significant decrease of the prostate-specific antigen, even in those with levels between 4 and 10 ng/ml. This decrease seems to follow a logarithmic course but, because only three measurements during radiotherapy were made, this needs further study. With higher levels (more than 20 ng/ml), we rarely saw a value of less than 10 ng/ml at the end of radiotherapy but had to wait for several months for lower values to be reached. In several cases prostate-specific antigen decrease took up to three months after the end of the radiation course. Our results indicate that prostate-specific antigen values actually start decreasing during the radiation course itself and may, therefore, be useful for monitoring response to radiotherapy.

Short dialysis with a polyacrylonitrilmembrane (RP 6) without the use of a closed recirculating dialyzate delivery system.

Because of excessive eltrafiltration (UF), the RP 6 dialyzer requires a closed recirculating dialyzate delivery system. The purpose of this study is to present the characteristics of the RP 6 dialyzer on a single needle system which programs the UF rate of this dialyzer. The single needle system consists of one blood pu-mp and two roller pump heads, switched on and off at preselected maximum and minimum out let pressures (OP). It is possible to decrease the UF rate by lowering the OP in the bubble trap chamber. By varying OP from 0 to 100 mm Hg, we obtained an UF rate in vitro of 6.5 ml per minute. The clearance values, in ml/min, obtained at OP 0 to -100 NN Hg, QB 300 and QD 500 are (in ml/min): urea: 160.0, creatinine: 145.0, sucrose-C14: 105.4, sodiumiothalamate-i125: 79.9, cyanocobalamin-co58: 73.7 and inulin-3H: 40.7. The priming volume (corn-oil) at OP 0 to -100 MM Hg, QB 250, QD 500 varies between 140 ml (at the minimum OP) and 150 ml (at the maximum OP). We performed 370 dialyses. The dialysis runs were well tolerated: moderate hypotension occurred in 4% and cramps in 1.6% of the dialyses. In most cases no fluid perfusion was necessary. The residual blood volume (Technetium99m) is estimated at 8.2 ml(n equale 11).