Comparative targeting of human colon-carcinoma multicell spheroids using one- and two-step (bispecific antibody) techniques

Abstract

In the perspective of radioimmunotherapy (RIT) of micrometastases, we compared, in multicell spheroids (MS), the uptake and retention kinetics of 125I-F(ab)'2 F6 anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), and the affinity enhancement system (AES) using an anti-CEA/anti-DTPA-indium bispecific antibody (BsMAb) and a 125I-labeled di-DTPA-In-tyrosine-lysine bivalent hapten. We used MS of colorectal tumor cell lines expressing CEA strongly (LS 174T), weakly (HT-29) or not at all (HRT-18). Uptake and retention kinetics of 125I-F(ab)'2 F6 and 125I-BsMAb used alone gave similar results. The highest uptake values, obtained with LS 174T MS, were slightly lower with AES than with 125I-F(ab)'2 F6. However, effective retention half-lives were longer for AES than for 125I-F(ab)'2 F6 or for 111In-labeled monovalent hapten after pre-incubation of spheroids with BsMAb. Autoradiography showed the same slow and heterogeneous distribution of 125I-F(ab)'2 F6 and 125I-BsMAb. These results indicate that the 2-step technique is more favorable for RIT: uptake values were approximately the same but uptake kinetics were more rapid, and retention half-life was longer than with the one-step technique.

In vivo and in vitro inhibition of pancreatic cancer growth by targeted alpha therapy using 213Bi-CHX.A”-C595

“…12 As in vitro multicell spheroids (MCSs) resemble micrometastases during the avascular phase of their development, this model has applications for evaluation of the effectiveness of radioimmunotherapy of tumor micrometastases. [13][14][15][16][17] Spheroids can also resemble the in vivo situation with regard to cell shape and cellular environment, which in turn can determine gene expression and the biological behaviors of the cells.…”

The Development of the α-Particle Emitting Radionuclides 212Bi and 213Bi, and Their Decay Chain Related Radionuclides, for Therapeutic Applications

“…Autoradiography and histological samples of tumor models and normal tissue might improve on this. [98][99][100][101] Along with improvement of dosimetry for the clinical situation, cell survival probabilities after given numbers of R-particle traversals require a more accurate determination. The average cell survival probabilities derived from macroscopic dosimetry experiments may not reflect the true cell survival probabilities from R-particle traversals.…”

“…90 For evaluation of the applicability of a 212/213 Bi radiopharmaceutical toward a tumor model, multicellular spheroids have already been of substantial value. 91,99,127,150 Such a model system could be employed for evaluation and optimization of carrier molecule tumor kinetics (e.g., influence of size, pI, and affinity), 83 for studying tumor sterilization/ growth retardation after different radioactivity levels and radionuclide distributions, and investigating the effect of repeated 212/213 Bi conjugate incubations.…”