ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO154

Urinary NGAL (uNGAL) as a Biomarker to Predict Late Nephrotoxicity in Pre-Clinical Models of Peptide-Based Radioligand Therapy (PRRT) for Cancer

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Vasquez Martinez, Gabriela, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Li, Mengshi, Viewpoint Molecular Targeting, Inc., Coralville, Iowa, United States
  • Rastogi, Prerna, The University of Iowa Hospitals and Clinics Department of Pathology, Iowa City, Iowa, United States
  • Liu, Dijie, Viewpoint Molecular Targeting, Inc., Coralville, Iowa, United States
  • Linn, Sarah C., The Ohio State University College of Veterinary Medicine, Columbus, Ohio, United States
  • Mayoral Andrade, Gabriel, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Schultz, Michael King, Viewpoint Molecular Targeting, Inc., Coralville, Iowa, United States
  • Zepeda-Orozco, Diana, Nationwide Children's Hospital, Columbus, Ohio, United States
Background

PRRT for cancer has gained traction in oncology due to favorable tumor-targeting performance. A dose limiting organ for most PRRTs is the kidney, and toxicity is thought to be caused by proximal-tubule reabsorption of radiolabeled peptide. The objective of this study was to evaluate the use of uNGAL to predict chronic renal damage after PRRT therapy in a murine pre-clinical model

Methods

We conducted a PRRT dose escalation study to anticipated renal injury levels in CD-1 Elite mice (0.9, 3 and 6.7 MBq of a 212Pb labeled peptide, n = 6 per group). Urine was collected on days 1, 3, 53, and at 7 months. Serum was collected on weeks 1, 5, 8, and at 7 months. Mice were euthanized at 7 months for histology. NGAL was measured by ELISA. BUN and Creatinine were measured by blood chemistry panel. Histological tubular injury (TI), interstitial inflammation (IF), glomerulosclerosis (GS) and interstitial fibrosis (FIB) scores (0 to 5) were performed by pathologist in PAS and trichrome stained sections

Results

uNGAL concentration was higher with increasing dosages of the 212Pb labeled peptide 24 hours after therapy (Table 1). High PRRT dose of the 212Pb labeled peptide (6.7 MBq) resulted on late TI, IF, GS and FIB (2.6+1.34, 2.2+1.095, 1.4+1.14, 3.2+0.836 respectively, p=<0.05). uNGAL positively correlated with alpha dose (r =0.89, p=<0.0001), TI (r=0.71, p=0.0001), IF (r=0.65, p=0.0008) and FIB (r=0.75, p=<0.0001). BUN and creatinine were significantly increased at 7 months with high PRRT doses (Table1) but not significantly different at 1, 5 or 8 weeks.

Conclusion

uNGAL could be a potential early biomarker to predict the progression of AKI to CKD after PRRTs. Comparisons to other radionuclides are needed to develop a more detailed understanding.

Kidney Function and Urine Biomarkers
Kidney Function/Urine BiomarkerControl0.9 MBq3.0 MBq6.7 MBq
uNGAL at 24 hrs (ng/ml) 34.72 ± 11.46301.40 ± 133.49 *663.01 ± 181.48 ***1178.62 ± 661.80 *
BUN at 7 months (mg/dl)16.33 ± 1.8622.20 ± 6.9724.33 ± 8.59 **34.20 ± 9.60 ****
sCreatinine at 7 months (mg/dl)0.10 ± 0.000.10 ± 0.070.26 ± 0.15 **0.38 ± 0.20 ****

BUN: Blood Nitrogen Urea, NGAL: Neutrophil gelatinase-associated lipocalin, MBq: Megabecquerel; Mean ± Standard deviation, *p=<0.05, **p=0.01, ***p=<0.001, ****p=<0.0001

Funding

  • Other NIH Support