Comparative study of biodistribution of PEG-modified radioiodinated poly (n-isopropyl acrylamide) with that of non-pegylated based thermoresponsive polymer for localized radiotherapy

PEGylation is one of several approaches that have been successfully applied to large molecules to improve their pharmacokinetics. In this study, we report the improved effect on the retention of the radiolabeled thermoresponsive polymer on intratumoral injection in Swiss mice by way of self-assembly of PEGylated-¹²⁵I-Poly (N- Isopropyl acrylamide) (PNIPAM) polymer instead of chemical activation. This was done essentially to retain the retention property of the thermoresponsive polymer and enhance the radiotherapeutic effect of the radioiodinated polymer. Two groups of Swiss mice (6-8 weeks age) (n = 3) for each time point were induced fibrosarcoma tumor by injecting ~10⁶ tumor cells in 150 μL sterile normal saline into the left lateral thigh muscles. The animals with tumor of ~1 cm diameter were selected for the study. Biodistribution as well as excretion patterns obtained by PEGylated-¹²⁵I-PNIPAM polymer at 2 h, 1, 4, and 7 days post injection (p.i.) (n = 3) were compared with those obtained by non-PEGylated-¹²⁵I–PNIPAM polymer. To ensure the in-vivo retention of PEGylated-¹²⁵I-PNIPAM polymer, another set of Swiss mice (n = 3) bearing fibrosarcoma tumor were injected with PEGylated polymer intratumorally at multiple sites for obtaining planar images at 1 h, 3 h, 1, 3 and 5 days p.i. using preclinical small animal imaging gamma scanner. The biodistribution of PEG modified radioiodinated polymer was found to be increased within the tumor (44 ± 1.23%) (n = 3) as compared to that of non-PEGylated- ¹²⁵I-PNIPAM polymer (32 ± 2.18%) (n = 3) at 2 h p.i. decreasing slowly to 10 ± 1.39% of the injected activity within 5 days p.i. No substantial organ-specific accumulation of the radioactivity released from the injected site, i.e. the tumor was observed. Most of the radioiodinated polymer was excreted through urine as compared to the non-PEGylated- ¹²⁵I-PNIPAM polymer. Planar imaging of mice bearing fibrosarcoma tumor (n = 3) when injected with PEGylated-¹²⁵I-tyrosinamide PNIPAM intratumorally (~150 μCi) showed good retention at the injected site up to 5 days. The results indicate that PEGylation of the radioiodinated thermo-responsive PNIPAM polymer showed a considerable promise as an agent of choice for localized tumor radiotherapy. (author)