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Research ArticleBasic Science Investigation

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

Marleen Melis, Jan de Swart, Monique de Visser, Saskia C. Berndsen, Stuart Koelewijn, Roelf Valkema, Otto C. Boerman, Eric P. Krenning and Marion de Jong
Journal of Nuclear Medicine December 2010, 51 (12) 1962-1968; DOI: https://doi.org/10.2967/jnumed.110.080143
Marleen Melis
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Jan de Swart
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Monique de Visser
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Saskia C. Berndsen
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Stuart Koelewijn
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Roelf Valkema
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Otto C. Boerman
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Eric P. Krenning
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Marion de Jong
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  • FIGURE 1.
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    FIGURE 1.

    Blood enters functional units of kidneys, the nephrons, via afferent arteriole (AA) of renal artery. In the capillary network in glomerulus (G), waste and useful molecules are filtered from blood and transported into proximal tubules (PT). Waste molecules are excreted in primary urine via loop of Henle (LH) and distal tubules (DT) into collecting duct (CD) leading to renal pelvis and bladder. In first convoluted part of PT, megalin/cubilin receptors are expressed, playing a significant role in reabsorption of useful molecules. Extraction from blood in efferent arteriole (EA) (27) directly into PT is another route of excretion of molecules into urine, which is the most prominent way of 99mTc-MAG3 clearance. 111In-DTPA is cleared only via glomerular filtration and is directly excreted into urine, whereas 99mTc-DMSA is partly filtrated in glomeruli, followed by partial reabsorption in PT. 99mTc-DMSA is also partially peritubularly extracted from blood, primarily in last straight part of PT, which may extend into outer medulla of kidney. RV = renal vein.

  • FIGURE 2.
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    FIGURE 2.

    Typical images of maximum-intensity projections and coronal slices of kidney after 99mTc-DMSA scintigraphy performed at day 140 after therapy in nontreated control, PRRT-treated, or PRRT + lysine–treated rats. Ex vivo autoradiograms are of frozen kidney sections, prepared immediately after imaging. MIP = maximum-intensity projection. Lys = lysine.

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    FIGURE 3.

    (A and B) Renography after injection of 50 MBq of 99mTc-MAG3, expressed as %IA/kidney (A) and %IA/cm3 cortex (B). (C) Renography after injection of 50 MBq of 111In-DTPA, expressed as %IA/kidney. (D) Typical example of a maximum-intensity-projection dual-isotope image in control rats, 6 min after injection: 99mTc-MAG3 (left), 111In-DTPA (middle), and merged (right) images. Lys = lysine.

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    TABLE 1

    Overview of Results in Control, PRRT, and PRRT + Lysine Rats

    ParameterDays after therapyControl (P control vs. PRRT)PRRT (P PRRT vs. PRRT + lysine)PRRT + lysine (P control vs. PRRT + lysine)
    177Lu uptake (MBq/kidney)4—3.8 ± 0.3*2.0 ± 0.1
    BW, % vs. day 090134 ± 3*111 ± 6†127 ± 5‡
    140143 ± 4*113 ± 11†138 ± 6, NS
    Protein in urine (mg/24 h)10011 ± 2*62 ± 9*22 ± 8*
    Urea in serum (mmol/L)905.8 ± 0.2*10.5 ± 2.2‡7.2 ± 1.0†
    1405.3 ± 0.5*32.6 ± 9.4*7.3 ± 0.6*
    Creatinine in serum (μmol/L)9021 ± 2*60 ± 5*37 ± 3*
    14024 ± 1*108 ± 20*35 ± 4*
    Grading histologic renal damage1400.4 ± 0.6*4 ± 0*1.3 ± 0.5‡
    99mTc-DMSA (%IA/kidney)9013.7 ± 1.4*6.4 ± 2.4*12.5 ± 1.2, NS
    14018.1 ± 1.9*5.6 ± 3.2*14.3 ± 1.1†
    99mTc-MAG3 (%IA/kidney, 2–6 min)100–12013.1 ± 2.6*4.3 ± 1.5*8.5 ± 1.6*
    99mTc-MAG3 (%IA/cm3 cortex, 2–6 min)100–1206.9 ± 1.9*2.6 ± 1.3‡3.8 ± 1.0*
    111In-DTPA (%IA/kidney, 2–4 min)100–1204.7 ± 1.0†2.1 ± 1.4, NS4.4 ± 0.6, NS
    • ↵* P < 0.0001.

    • ↵† P < 0.001.

    • ↵‡ P < 0.05.

    • NS = not significant.

    • Quantification of retained renal radioactivity was expressed as total MBq/kidney for 177Lu and %IA/kidney for 99mTc-DMSA. Peak activity was expressed as %IA/kidney for 111In-DTPA and 99mTc-MAG3 or as %IA/cm3 cortex for 99mTc-MAG3. BW of rats was expressed as percentage of BW at day 0. Protein loss in urine was expressed in mg/24-h urine. Serum urea and creatinine content was expressed in mmol/L or μmol/L. Histologic grading of renal damage was expressed on a scale of 0–4.

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Journal of Nuclear Medicine: 51 (12)
Journal of Nuclear Medicine
Vol. 51, Issue 12
December 1, 2010
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Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After 177Lu-Labeled Tyr3-Octreotate Radionuclide Therapy
Marleen Melis, Jan de Swart, Monique de Visser, Saskia C. Berndsen, Stuart Koelewijn, Roelf Valkema, Otto C. Boerman, Eric P. Krenning, Marion de Jong
Journal of Nuclear Medicine Dec 2010, 51 (12) 1962-1968; DOI: 10.2967/jnumed.110.080143

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Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After 177Lu-Labeled Tyr3-Octreotate Radionuclide Therapy
Marleen Melis, Jan de Swart, Monique de Visser, Saskia C. Berndsen, Stuart Koelewijn, Roelf Valkema, Otto C. Boerman, Eric P. Krenning, Marion de Jong
Journal of Nuclear Medicine Dec 2010, 51 (12) 1962-1968; DOI: 10.2967/jnumed.110.080143
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