Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After Lu-177-Labeled Tyr(3)-Octreotate Radionuclide Therapy

作者：Melis Marleen^*; de Swart Jan; de Visser Monique; Berndsen Saskia C; Koelewijn Stuart; Valkema Roelf; Boerman Otto C; Krenning Eric P; de Jong Marion

来源：Journal of Nuclear Medicine, 2010, 51(12): 1962-1968.

DOI：10.2967/jnumed.110.080143

• animal imaging
• radionuclide therapy
• renal
• PRRT
• dynamic imaging
• micro-SPECT
• nephrotoxicity
• renography

High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with beta-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal radiation dose. In rat PRRT studies, renal protection by the coadministration of lysine was confirmed by histologic examination of kidney specimens indicating nephrotoxicity. In the current study, we investigated dedicated small-animal SPECT/CT renal imaging in rats to monitor renal function in vivo during follow-up of PRRT, with and without lysine. Methods: The following 3 groups of rats were imaged using a multipinhole SPECT/CT camera: controls (group 1) and rats at more than 90 d after therapy with 460 MBq (15 mu g) of Lu-177-DOTA-Tyr(3)-octreotate without (group 2) or with (group 3) a 400-mg/kg lysine coinjection as kidney protection (n >= 6 per group). At 90 and 140 d after therapy, static kidney scintigraphy was performed at 2 h after injection of 25 MBq of Tc-99m-dimercaptosuccinic acid (Tc-99m-DMSA). In addition, dynamic dual-isotope renography was performed using 50 MBq of In-111-diethylenetriaminepentaacetic acid (In-111-DTPA) and 50 MBq of Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) at 100-120 d after therapy. Results: In-111-DTPA and Tc-99m-MAG3 studies revealed a time-activity pattern comparable to those in patients, with a peak at 2-6 min followed by a decline of renal radioactivity. Reduced In-111-DTPA, Tc-99m-MAG3, and Tc-99m-DMSA uptake indicated renal damage in group 2, whereas group 3 showed only a decrease of Tc-99m-MAG3 peak activity. These results indicating nephrotoxicity in group 2 and renal protection in group 3 correlated with levels of urinary protein and serum creatinine and urea and were confirmed by renal histology. Conclusion: Quantitative dynamic dual-isotope imaging using both In-111-DTPA and Tc-99m-MAG3 and static Tc-99m-DMSA imaging in rats is feasible using small-animal SPECT, enabling longitudinal monitoring of renal function. Tc-99m-MAG3 renography, especially, appears to be a more sensitive marker of tubular function after PRRT than serum chemistry or Tc-99m-DMSA scintigraphy.

• 出版日期2010-12-1