Abstract
Urinary NGAL (uNGAL) as a Biomarker to Predict Late Nephrotoxicity in Pre-Clinical Models of Peptide-Based Radioligand Therapy (PRRT) for Cancer: SA-PO154
Journal of the American Society of Nephrology, Vol.33(11S), pp.644-645
11/2022
DOI: 10.1681/ASN.20223311S1644c
Abstract
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.
Conclusions:
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.
Details
- Title: Subtitle
- Urinary NGAL (uNGAL) as a Biomarker to Predict Late Nephrotoxicity in Pre-Clinical Models of Peptide-Based Radioligand Therapy (PRRT) for Cancer: SA-PO154
- Creators
- Gabriela Vasquez Martinez - Nationwide Children's HospitalMengshi Li - Viewpoint Molecular TargetingPrerna Rastogi - University of IowaDijie Liu - Viewpoint Molecular TargetingSarah C. Linn - The Ohio State UniversityGabriel Mayoral Andrade - Nationwide Children's HospitalMichael K. Schultz - University of IowaDiana Zepeda-Orozco - The Ohio State University
- Resource Type
- Abstract
- Publication Details
- Journal of the American Society of Nephrology, Vol.33(11S), pp.644-645
- DOI
- 10.1681/ASN.20223311S1644c
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Language
- English
- Date published
- 11/2022
- Academic Unit
- Pathology; Radiology; Radiation Oncology
- Record Identifier
- 9984649050702771
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