Safety and Efficacy of Para-Aminohippurate Coinfusion for Renal Protection During Peptide Receptor Radiotherapy in Patients with Neuroendocrine Tumors

Alexandros Moraitis; Walter Jentzen; Pedro Fragoso Costa; David Kersting; Stephan Himmen; Marta Coelho; Marian Meckel; Cees J A van Echteld; Wolfgang P Fendler; Ken Herrmann; Miriam Sraieb

doi:10.2967/jnumed.123.266619

Safety and Efficacy of Para-Aminohippurate Coinfusion for Renal Protection During Peptide Receptor Radiotherapy in Patients with Neuroendocrine Tumors

J Nucl Med. 2024 Apr 18:jnumed.123.266619. doi: 10.2967/jnumed.123.266619. Online ahead of print.

Authors

Alexandros Moraitis^{1

2}, Walter Jentzen^{3

2}, Pedro Fragoso Costa^{3

2}, David Kersting^{3

2}, Stephan Himmen^{3

2}, Marta Coelho^{3

2}, Marian Meckel⁴, Cees J A van Echteld⁵, Wolfgang P Fendler^{3

2}, Ken Herrmann^{3

2}, Miriam Sraieb^{3

2}

Affiliations

¹ Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; alexandros.moraitis@uk-essen.de.
² German Cancer Consortium, Partner Site University Hospital Essen, Essen, Germany.
³ Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁴ ITM Isotope Technologies Munich SE, Garching/Munich, Germany; and.
⁵ Helacor Consultancy, Oberwil, Switzerland.

PMID: 38637142
DOI: 10.2967/jnumed.123.266619

Abstract

Para-aminohippurate, also known as p-aminohippuric acid (PAH), is used clinically to measure effective renal plasma flow. Preclinically, it was shown to reduce ¹⁷⁷Lu-DOTATOC uptake in the kidneys while improving bioavailability compared with amino acid (AA) coinfusion. We report the safety and efficacy of PAH coinfusion during peptide receptor radiotherapy in patients with neuroendocrine tumors. Methods: Twelve patients with metastatic or unresectable gastroenteropancreatic neuroendocrine tumors received ¹⁷⁷Lu-DOTATOC in 33 treatment cycles. Either 8 g of PAH or a mixture of 25 g of arginine and 25 g of lysine were coinfused. Safety was assessed by monitoring laboratory data, including hematologic and renal data, as well as electrolytes obtained before and 24 h after treatment. For radiation dosimetry, whole-body scans were performed at 1, 24, and 48 h and a SPECT/CT scan was performed at 48 h, along with blood sampling at 5 min and 0.5, 2, 4, 24, and 48 h after administration. Absorbed dose estimations for the kidneys and bone marrow were performed according to the MIRD concept. Results: In 15 treatment cycles, PAH was coinfused. No changes in mean creatinine level, glomerular filtration rate, and serum electrolytes were observed before or 24 h after treatment when using PAH protection (P ≥ 0.20), whereas serum chloride and serum phosphate increased significantly under AA (both P < 0.01). Kidney-absorbed dose coefficients were 0.60 ± 0.14 Gy/GBq with PAH and 0.53 ± 0.16 Gy/GBq with AA. Based on extrapolated cumulative kidney-absorbed doses for 4 cycles, 1 patient with PAH protection and 1 patient with AA protection in our patient group would exceed the 23-Gy conservative threshold. The bone marrow-absorbed dose coefficient was 0.012 ± 0.004 Gy/GBq with PAH and 0.012 ± 0.003 Gy/GBq with AA. Conclusion: PAH is a promising alternative to AA for renal protection during peptide receptor radiotherapy. Further research is required to systematically investigate the safety profile and radiation dosimetry at varying PAH plasma concentrations.

Keywords: NET; PAH; PRRT; dosimetry; renal protection.