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
- Onconephrology: Clinical and Research Advances - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
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 Biomarker | Control | 0.9 MBq | 3.0 MBq | 6.7 MBq |
| uNGAL at 24 hrs (ng/ml) | 34.72 ± 11.46 | 301.40 ± 133.49 * | 663.01 ± 181.48 *** | 1178.62 ± 661.80 * |
| BUN at 7 months (mg/dl) | 16.33 ± 1.86 | 22.20 ± 6.97 | 24.33 ± 8.59 ** | 34.20 ± 9.60 **** |
| sCreatinine at 7 months (mg/dl) | 0.10 ± 0.00 | 0.10 ± 0.07 | 0.26 ± 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 – Viewpoint