Two routes for 99mTc-DMSA uptake into the renal cortical tubular cell

Abstract

Critical factors determining the renal handling of 99mTc-dimercaptosuccinic acid (DMSA) are protein binding in plasma and the renal 99mTc-DMSA extraction efficiency. Comparison of the count rate over soft tissue with that over the cardiac blood pool about 1 h after injection demonstrated that 99mTc-DMSA is not exclusively an intravascular label. 99mTc-DMSA was 76% protein bound in plasma as demonstrated by HPLC and gel filtration. Assuming that the 24% that is not protein bound is filtered at the glomerulus, the renal extraction efficiency of 99mTc-DMSA by glomerular filtration is about 5%. Since the total renal extraction efficiency was also found to be about 5%, the majority of the activity that becomes fixed in the renal cortex arrives there as a result of filtration followed by tubular reabsorption rather than by direct extraction from peritubular blood. However, discordant changes in DMSA and DTPA uptake induced by captopril in renovascular hypertension (RVH) suggested that a minority of uptake was by direct peritubular extraction. This kinetic model was supported by indirect measurement of protein binding and extraction efficiency based on the kinetics of 99mTc-DMSA disappearance from plasma and kinetics of uptake in the kidneys. Furthermore, differential functional studies based on 99mTc-DMSA and 99mTc-DTPA before and after captopril in patients with RVH due to unilateral renal artery stenosis confirmed filtration followed by tubular reabsorption as the predominant route for DMSA uptake by the kidney.

Renal Uptake of 99mTc-Dimercaptosuccinic Acid Is Dependent on Normal Proximal Tubule Receptor–Mediated Endocytosis

“…In the case of heavy proteinuria, an altered tracer distribution could be due to the increased glomerular filtration of proteins, leading to increased urinary loss and reduced 99m Tc-DMSA uptake, as reported (36). Conversely, diminished filtration would lead to low 99m Tc-DMSA kidney uptake, even while tubular function is retained, as it is observed under renal artery stenosis and captopril experiments (5,37). Thus, 99m Tc-DMSA renal uptake should also be cautiously interpreted in the case of alterations in glomerular filtration.…”

“…The sodium-dependent dicarboxylate transporter NaDC-3 has been implicated in the basolateral uptake of 99m Tc-DMSA from peritubular capillaries into proximal tubule cells (13). The mechanism by which 99m Tc-DMSA may be reabsorbed from the glomerular ultrafiltrate is unknown; however, studies have indicated that this route may contribute substantially to the renal uptake of the tracer (4,5,14). The potential importance of this pathway is further stressed by recent observations of a decreased renal uptake of 99m Tc-DMSA in patients with proximal tubular endocytic dysfunctions, such as Dent's disease, Lowes syndrome, and Fanconi syndrome (10,15,16).…”

“…Two main routes of 99m Tc-DMSA tubular uptake have been proposed: by basolateral uptake from plasma by peritubular extraction and by tubular reabsorption from the glomerular ultrafiltrate. However, the significance of both routes is debated (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The sodium-dependent dicarboxylate transporter NaDC-3 has been implicated in the basolateral uptake of 99m Tc-DMSA from peritubular capillaries into proximal tubule cells (13).…”

Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After 177Lu-Labeled Tyr3-Octreotate Radionuclide Therapy

“…The 2 postulated mechanisms of 99m Tc-DMSA uptake are peritubular extraction or absorption of plasma protein-bound 99m Tc-DMSA directly from the blood into the proximal tubular cells or glomerular filtration, followed by tubular reabsorption. Discussions on the relative contribution of each of these pathways are ongoing (20)(21)(22)(23)(24)(25)(26). Dynamic imaging of the clearance of radiolabeled diethylenetriaminepentaacetic acid (DTPA) monitors glomerular filtration, because this small molecule is cleared only via this route.…”

Single-photon emission CT using99mTc-dimercaptosuccinic acid (DMSA) for characterization of suspected renal masses

“…Its main metabolic pathway first involves glomerular filtration, followed by tubular reabsorption, with minimal urinary excretion (5%). 2 In adults, its foremost clinical use is to determine differential renal function, but also to image ectopic renal tissue. 3 We have occasionally used Tc-DMSA scans to establish whether a suspected renal mass or pseudomass contains functioning renal tissue or not.…”