Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid Journal Article
| Authors: | He, P.; Kramer, K.; Smith-Jones, P.; Zanzonico, P.; Humm, J.; Larson, S. M.; Cheung, N. K. V. |
| Article Title: | Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid |
| Abstract: | Purpose: Radioimmunotherapy (RIT) using 131I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of 131I-3F8 and to identify limiting factors that may impact therapeutic ratio. Methods: Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[C IAR]), (2) that of the unbound antibody AUC[CIA], and (3) their therapeutic ratio (AUC[CIAR]/AUC[CIA]). Results: Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R=0.95±0.03). Correlations were substantially better when compared to the one-compartment model (R=0.92±0.11 versus 0.77±0.21, p=0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of 131I-3F8 from 10% to 90% increased both (AUC[CIAR]) and therapeutic ratio ([AUC[CIAR]/AUC[C IA]] by 7.4 fold, (2) When extrapolated to the clinical setting, the model predicted that if 131I-3F8 could be split into 4 doses of 1.4 mg each and given at ≥24 hours apart, an antibody affinity of KD of 4×10-9 at 50% immunoreactivity were adequate in order to deliver ≥100 Gy to tumor cells while keeping normal CSF exposure to <10 Gy. Conclusions: This model predicted that immunoreactivity, affinity and optimal scheduling of antibody injections were crucial in improving therapeutic index. © 2010 Springer-Verlag. |
| Keywords: | cerebrospinal fluid; radioimmunotherapy; pharmacokinetics; optimization; 3f8; intra-ommaya |
| Journal Title: | European Journal of Nuclear Medicine and Molecular Imaging |
| Volume: | 38 |
| Issue: | 2 |
| ISSN: | 1619-7070 |
| Publisher: | Springer |
| Date Published: | 2011-02-01 |
| Start Page: | 334 |
| End Page: | 342 |
| Language: | English |
| DOI: | 10.1007/s00259-010-1633-8 |
| PROVIDER: | scopus |
| PMCID: | PMC3278084 |
| PUBMED: | 20936407 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: EJNMA" - "Source: Scopus" |
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