Biodistribution and Pharmacokinetics of 99mTc-Labeled Rhizophora Mangle Extract: Renal Clearance and Systemic Behavior
Joao Victor Braga Alves Peixoto, Natália Cristina Gomes da Silva, Jessica Ingrid Faria de Souza, Ralph Santos-Oliveira, Catharina Eccard FingoloIntroduction:
Rhizophora mangle (Rhizophoraceae) is a mangrove species of ethnopharmacological significance, rich in polyphenols, flavonoids, and tannins. Despite preclinical evidence of its biological activities, in vivo pharmacokinetic characterization remains lacking. Technetium-99m (⁹⁹ᵐTc) radiolabeling offers a robust approach to assess systemic biodistribution and clearance dynamics of plant extracts.
Methods:
A hydroethanolic extract of R. mangle leaves was radiolabeled with ⁹⁹ᵐTc using stannous chloride at pH 5.5–6.0. Radiochemical purity was evaluated by Radio-Thin Layer Chromatography (RTLC). Male Wistar rats received an intraperitoneal injection of the labeled extract. At 24 hours post-injection, organ biodistribution was quantified using gamma counting. For pharmacokinetics, blood samples were collected at multiple time points up to 24 hours, and Non-Compartmental Analysis (NCA) was performed to determine key parameters.
Results:
Radiolabeling achieved > 97% purity with stable labeling over 24 hours. The extract showed predominant renal accumulation (kidneys: 0.0191 %ID/g) and notable bladder deposition, with minimal hepatic uptake and negligible brain penetration. Pharmacokinetic analysis revealed low systemic retention (C₀: 2.71×10⁻¹⁰ mg/mL), rapid clearance (CL: 0.038 L/h), a low volume of distribution (Vd: 0.268 L), and a short elimination half-life (t₁/₂ = 4.9 h).
Discussion:
The observed renal excretion profile aligns with the extract's hydrophilic polyphenolic composition and supports its suitability for applications requiring efficient elimination. The low systemic retention and absence of accumulation in reticuloendothelial organs suggest favorable pharmacokinetics for diagnostic or transient therapeutic use. However, the absence of intravenous comparison precludes bioavailability assessment, and results are limited to healthy models.
Conclusion:
⁹⁹ᵐTc-labeled R. mangle extract demonstrates high radiochemical stability, preferential renal clearance, and rapid systemic elimination in vivo. These features support its biocompatibility and potential for renal imaging or short-duration therapeutic delivery. Further studies in pathological models and advanced formulation systems are required to explore its translational viability.