Kidney Week

Abstract: TH-PO1140

Early Urinary Biomarker to Identify Tolerable Radioligand Therapy Dosing: A Pilot Study

Session Information

• Onconephrology: Emerging Biomarkers, Preclinical Models, Clinical Challenges, and Therapeutic Strategies
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1600 Onconephrology

Authors

• Pulliam, Casey F., Nationwide Children's Hospital, Columbus, Ohio, United States

Casey F. Pulliam, PhD

• Robles-Planells, Claudia J., Nationwide Children's Hospital, Columbus, Ohio, United States

Claudia J. Robles-Planells, PhD

• Chena-Becerra, Florencia, Nationwide Children's Hospital, Columbus, Ohio, United States

Florencia Chena-Becerra, PhD

• Vasquez Martinez, Gabriela, Nationwide Children's Hospital, Columbus, Ohio, United States

Gabriela Vasquez Martinez, PhD

• Mayoral Andrade, Gabriel, Nationwide Children's Hospital, Columbus, Ohio, United States

Gabriel Mayoral Andrade, MD, PhD

• Schultz, Michael King, Perspective Therapeutics, Coralville, Iowa, United States

Michael King Schultz, MS, PhD

• Zepeda-Orozco, Diana, Nationwide Children's Hospital, Columbus, Ohio, United States

Diana Zepeda-Orozco, MD, MS

Background

[²¹²Pb]VMT-α-NET (²¹²Pb-VMT) is a novel peptide-based α-emitting targeted radioligand therapy (TRT) for SSTR2-positive tumors with promising clinical safety and tumor control. Nonspecific tubular TRT uptake can cause long-term kidney toxicity, limiting clinical dose escalation. Previous studies showed that 4.4 MBq of ²¹²Pb-VMT in ARJ42 tumor-bearing immunocompromised mice yielded complete responses, 90-day survival, and good weight tolerance (Liu et al., EANM). This pilot study evaluates early tubular urinary biomarkers to predict late-onset kidney functional decline, using a dose-escalation TRT model.

Methods

To identify a ²¹²Pb-VMT dose that would induce kidney injury, male C57BL/6J mice (8-10 wks old, n=3-5) received a single IV dose of vehicle control or ²¹²Pb-VMT (3.7 or 5.6 MBq; 38.9-55.5 Gy RBE-weighted kidney dose). Urinary biomarkers kidney injury molecule-1 (uKIM1), neutrophil gelatinase-associated lipocalin (uNGAL), and epidermal growth factor (uEGF) were measured on days 1 (D1) and 36 (D36) and normalized to urine creatinine (uCr). Functional biomarkers, blood urea nitrogen (BUN) and serum cystatin C, were assessed on D1 and D36, and transdermal GFR (tGFR) was measured on D36, prior to euthanasia. At D36, kidney tissue was analyzed for KIM1 (tKIM1) and NGAL (tNGAL) protein expression and paraffin-embedded for blinded histological scoring.

Results

There were no significant differences in histological changes, tGFR, BUN, or cystatin C on D36 between treated mice and controls. At D36, tKIM1 was increased in treated mice (Veh= 12.9; 3.7 MBq= 81.7; 5.6 MBq= 118.6 pg/mg protein; p<0.05) and tNGAL only with 5.6 MBq (p<0.05) compared with controls. D1 uNGAL was elevated (Veh=85.8; 3.7 MBq= 481.9; 5.6 MBq= 642.7 ng/mg uCr; p<0.01), D1 uEGF was reduced (vehicle=5.3; 3.7 MBq=2.6; 5.6 MBq=1.9 ug/mg uCr; p<0.01) and D36 uKIM1 increased (Veh=4.8; 3.7 MBq=27.8; 5.6 MBq=54.4 ng/mg uCr; p<0.01) in treated mice compared with controls. The injected dose strongly correlated (p<0.001) with D1 uNGAL (r=0.87), D1 uEGF (r=-0.95), D36 uKIM1 (r=0.88), and D36 tKIM1 (r=0.82). D1 uNGAL (r=0.83, p=0.001) and uEGF (r=-0.79, p=0.004) also significantly correlated with D36 tKIM1 levels.

Conclusion

Our findings evidence that changes in uNGAL and uEGF one day post-²¹²Pb-VMT are associated with tubular injury detected one month after therapy, warranting further study to link these markers to late-onset functional decline.

Funding

• Other NIH Support