Suprachoroidal Injection of Topotecan for Retinoblastoma: A Preclinical Study.
Suprachoroidal topotecan achieved retinal drug levels far exceeding the toxic threshold for retinoblastoma cells.
Suprachoroidal Injection of Topotecan for Retinoblastoma: A Preclinical Study.
To assess whether levels of topotecan that are expected to be therapeutic against retinoblastoma tumors can be achieved within the retina and choroid by suprachoroidal injection (suprachoroidal injection) and to assess toxicity and safety in vivo.
Pharmacokinetics and dose escalation toxicity study.
retinal drug levels far exceeded what's needed to kill retinoblastoma cells
Following a single suprachoroidal injection of 50 μg topotecan, high levels of topotecan were achieved rapidly in both the retina and choroid.
Half-life (T 1/2 ) in the retina was 24.8 minutes.
Choroidal levels were 3.3-fold higher than retina with a similar rapid decline pattern.
Plasma (mean 4.3±2.6 ng/ml) and aqueous (peak at 120 min, mean 87 ng/ml) levels remained low throughout the study.
A single suprachoroidal injection of topotecan (50 μg/0.05 ml) achieved selective tissue distribution of its lactone moiety (retina/plasma, 1377.8) that was 23-fold higher than that reported with intraarterial chemotherapy (58.9) and more than 1000-fold higher than intravenous chemotherapy (1.32).
These retinal levels were nontoxic and were 885-fold higher than the known topotecan IC50 for human retinoblastoma cells (IC50 14 ng/gm).
Our findings support potential benefit of suprachoroidal injection of topotecan for patients with retinoblastoma.