Dosimetry Study of [I-131] and [I-125]-Meta-Iodobenzyl Guanidine in a Simulating Model for Neuroblastoma Metastasis

Abstract

The physical properties of I-131 may be suboptimal for the delivery of therapeutic radiation to bone marrow metastases, which are common in the natural history of neuroblastoma. In vitro and preliminary clinical studies have implied improved efficacy of I-125 relative to I-131 in certain clinical situations, although areas of uncertainty remain regarding intratumoral dosimetry. This prompted our study using human neuroblastoma multicellular spheroids as a model of metastasis. 3D dose calculations were made using voxel-based Medical Internal Radiation Dosimetry (MIRD) and dose-point-kernel (DPK) techniques. Dose distributions for I-131 and I-125 labeled mIBG were calculated for spheroids (metastases) of various sizes from 0.01 cm to 3 cm diameter, and the relative dose delivered to the tumors was compared for the same limiting dose to the bone marrow. Based on the same data, arguments were advanced based upon the principles of tumor control probability (TCP) to emphasize the potential theoretical utility of I-125 over I-131 in specific clinical situations. I-125-mIBG can deliver a higher and more uniform dose to tumors compared to I-131 mIBG without increasing the dose to the bone marrow. Depending on the tumor size and biological half-life, the relative dose to tumors of less than 1 mm diameter can increase several-fold. TCP calculations indicate that tumor control increases with increasing administered activity, and that I-125 is more effective than I-131 for tumor diameters of 0.01 cm or less. This study suggests that I-125-mIBG is dosimetrically superior to I-131-mIBG therapy for small bone marrow metastases from neuroblastoma. It is logical to consider adding I-125-mIBG to I-131-mIBG in multi-modality therapy as these two isotopes could be complementary in terms of their cumulative dosimetry.

Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids

“…Compared to human tissue samples, cultured tumor cell lines are easier to use, and widely available. Numerous tumor cell lines have been established and well-characterized, and also imple-mented in studying radiopharmaceuticals for MRT (see e. g. [8,9]). In these studies, however, the activity has often been assumed to distribute homogeneously in the cells, and there is uncertainty of how to include the dose equivalent from radiopharmaceuticals to assessed endpoints such as spheroid control probability (SCP, the dose-dependent proportion of non-regrown spheroids after irradiation) and spheroid control dose 50% (SCD 50 , the irradiation dose inducing 50% loss of spheroid regrowth).…”

“…In vitro three-dimensionally (3D-)cultured tumor cell aggregates, also known as spheroids, resemble their in vivo counterparts more closely than conventional two-dimensional (2D) cell culture systems; the cells cultured in 3D retain their natural architecture and functionality better than those cultured in 2D. Various culturing techniques have been exploited to create 3D tumor models to study tumor biology, pathogenesis as well as the effect of anti-cancer compounds [7], including radiopharmaceuticals used in MRT [8,9].…”

“…To exemplify, we simulate the behavior of activity vs. dose distributions in the case of the Auger electron and internal conversion (IC) electron emitters 125 I and 111 In, and the low-energy b electron emitter 177 Lu, all of which have very distinct spectra of the emitted electron and photon radiation [15]. 125 I is a radionuclide that has been studied widely regarding multicellular dosimetry [9] and it can be considered as a benchmark (''a model Auger emitter") although its clinical applications for MRT have been limited. On the other hand, 177 Lu is actively used today for MRT in PRRT, and also in e.g.…”