Development of a method to measure kinetics of radiolabelled monoclonal antibody in human tumour with applications to microdosimetry: positron emission tomography studies of iodine-124 labelled 3F8 monoclonal antibody in glioma

Abstract

We present a method to assess quantitatively the immunological characteristics of tumours using radiolabelled monoclonal antibody and positron emission tomography (PET) to improve dosimetry for radioimmunotherapy. This method is illustrated with a glioma patient who was injected with 96.2 MBq of iodine-124 labelled 3F8, a murine antibody (IgG3) specific against the ganglioside GD2. Serial PET scans and plasma samples were taken over 11 days. A three-compartment model was used to estimate the plasma to tumour transfer constant (K1), the tumour to plasma transfer constant k2, the association and dissociation constants (k3, k4) of antibody binding, and the binding potential. Tumour radioactivity peaked at 18 h at 0.0045% ID/g. The kinetic parameters were estimated to be: K1 = 0.048 ml h-1 g-1, k2 = 0.16 h-1, k3 = 0.03 h-1, k4 = 0.015 h-1 and BP = 2.25. Based on these kinetic parameters, the amount of tumour-bound radiolabelled monoclonal antibody was calculated. This method permits estimates of both macrodosimetry and microdosimetry at the cellular level based on in vivo non-invasive measurement.

Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer Fluorescence Molecular Imaging

“…For antibodies, which are approximately three times larger, K 1 is expected to be slower, on the order of 0.001 min −1 [7], which would correspond to an underestimation in k 3 of only 3 %. For this irreversible binding simulation study, the standard deviation in estimated k 3 was found to be equivalent to the standard deviation in the noise, i.e., the 2 % noise added to the targeted and untargeted curves yielded a percent-standard deviation in estimated k 3 of about 2 %.…”

“…(7)] to determine the accuracy and sensitivity of the algorithm for various levels of binding. This procedure was repeated for a slower K 1 = 0.001min −1 , to represent leakage rates of antibodies [7], with commonly used targeting agents (and employed in the animal experiment in this study), approximately three times larger (~150 kDa) than the 51-kDa dendrimer data that was used to approximate K 1 = 0.007 min −1 .…”

Monoclonal antibody ONS-M21 recognizes integrin α3 in gliomas and medulloblastomas

“…Some Abs were expected to have an antitumour effect by themselves (Dastider and Sharma, 1995), and others were used in combination with a radioisotope (Williams et al, 1990) or chemotherapeutic agent (Schrappe et al, 1992). Furthermore, some MAbs have also been applied to clinical diagnosis and therapies, even though these Abs were derived from mice (Daghighian et al, 1993;Schold et al, 1993;Faillot et al, 1996). Human Ab is preferred for clinical applications because mouse Ab can be more immunogenic than human Ab.…”

Preparation of the iodine‐124 derivative of the Bolton–Hunter reagent ([124I]I‐SHPP) and its use for labelling a VEGF antibody as a PET tracer

“…9 So far, investigators have used [ 124 I]iodine labelled antibodies to study malignancies such as breast cancer, 10,11 carcinoembryonic antigen-producing tumors, 12 colorectal cancer, 13 ovarian cancer, 14 and neuroblastoma. 15,16 It should be noted that all these papers are based on direct methods for labelling tyrosine residues of antibodies with iodine-124.…”