High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with β-particle-emitting radio-labeled 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 μg) of 177Lu-DOTA-Tyr3-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 99mTc-dimercaptosuccinic acid (99mTc-DMSA). In addition, dynamic dual-isotope renography was performed using 50 MBq of 111In-diethylenetriaminepentaacetic acid (111In-DTPA) and 50 MBq of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) at 100-120 d after therapy. Results: 111In-DTPA and 99mTc-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 111In-DTPA, 99mTc-MAG3, and 99mTc-DMSA uptake indicated renal damage in group 2, whereas group 3 showed only a decrease of 99mTc-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 111In-DTPA and 99mTc-MAG3 and static 99mTc-DMSA imaging in rats is feasible using small-animal SPECT, enabling longitudinal monitoring of renal function. 99mTc-MAG3 renography, especially, appears to be a more sensitive marker of tubular function after PRRT than serum chemistry or 99mTc-DMSA scintigraphy.

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Keywords Animal imaging, Dynamic imaging, Micro-SPECT, Nephrotoxicity, PRRT, Radionuclide therapy, Renal, Renography, animal experiment, animal model, animal tissue, article, controlled study, creatinine blood level, follow up, histopathology, kidney function, kidney injury, kidney scintiscanning, lutetium 177, lysine, male, mertiatide tc 99m, nephrotoxicity, nonhuman, octreotide[3 tyrosine], pentetate indium in 111, priority journal, protein urine level, radioactivity, rat, renal protection, single photon emission computer tomography
Persistent URL dx.doi.org/10.2967/jnumed.110.080143, hdl.handle.net/1765/23776
Citation
Melis, M.L, de Swart, J, de Visser, M, Berndsen, S.C, Koelewijn, S, Valkema, R, … de Jong, M. (2010). Dynamic and static small-animal SPECT in rats for monitoring renal function after177Lu-labeled Tyr3-octreotate radionuclide therapy. The Journal of Nuclear Medicine, 51(12), 1962–1968. doi:10.2967/jnumed.110.080143