title: Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy.
abstract: High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with β-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 μg) of (177)Lu-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 (99m)Tc-dimercaptosuccinic acid ((99m)Tc-DMSA). In addition, dynamic dual-isotope renography was performed using 50 MBq of (111)In-diethylenetriaminepentaacetic acid ((111)In-DTPA) and 50 MBq of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) at 100-120 d after therapy.
  
  
  RESULTS
  (111)In-DTPA and (99m)Tc-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 (111)In-DTPA, (99m)Tc-MAG3, and (99m)Tc-DMSA uptake indicated renal damage in group 2, whereas group 3 showed only a decrease of (99m)Tc-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.
  
  
  CONCLUSIONS
  Quantitative dynamic dual-isotope imaging using both (111)In-DTPA and (99m)Tc-MAG3 and static (99m)Tc-DMSA imaging in rats is feasible using small-animal SPECT, enabling longitudinal monitoring of renal function. (99m)Tc-MAG3 renography, especially, appears to be a more sensitive marker of tubular function after PRRT than serum chemistry or (99m)Tc-DMSA scintigraphy.
authors.affiliation: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. m.melis@erasmusmc.nl
authors.forename: Marleen
authors.initials: M
authors.lastname: Melis
authors.forename: Jan
authors.initials: J
authors.lastname: de Swart
authors.forename: Monique
authors.initials: M
authors.lastname: de Visser
authors.forename: Saskia C
authors.initials: SC
authors.lastname: Berndsen
authors.forename: Stuart
authors.initials: S
authors.lastname: Koelewijn
authors.forename: Roelf
authors.initials: R
authors.lastname: Valkema
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
mesh_terms: D000418:Albumins; D000818:Animals; D001345:Autoradiography; D003404:Creatinine / Q000097:blood; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000000981:diagnostic imaging / Q000502:physiology*; D007674:Kidney Diseases / Q000517:prevention & control; D007684:Kidney Tubules / Q000502:physiology; D008239:Lysine / Q000494:pharmacology; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use*; D004369:Pentetic Acid / Q000031:analogs & derivatives; D011507:Proteinuria / Q000378:metabolism; D011832:Radiation Injuries / Q000517:prevention & control; D011866:Radioisotope Renography; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D017263:Technetium Tc 99m Mertiatide; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D000418:Albumins; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C103803:indium DTPA-albumin; D017263:Technetium Tc 99m Mertiatide; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D004369:Pentetic Acid; C447941:lutetium Lu 177 dotatate; D003404:Creatinine; D008239:Lysine; D015282:Octreotide