Predicting the effectiveness of radioimmunotherapy against micrometastases: Kinetic modeling, marrow dosimetry and tumor control probability

Journal Article · Sun May 01 04:00:00 EDT 1994 · Journal of Nuclear Medicine

OSTI ID:197988

Willins, J D; Sgouros, G ^[1]

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1. Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

We have used tumor control probability (TCP) to assess mathematically the effectiveness of radioimmunotherapy (RIT) directed against blood-borne micrometastases. The differential equations governing antibody (Ab) diffusion and binding to antigen sites within a spherical micrometastases are solved, and the internal distribution of cumulated activity computed. This distribution is convolved with an electron dose kernel to yield the dose at any desired point. A two-compartment model of whole-body Ab kinetics is used to evaluate the red-marrow dose. The cluster dose is then resealed to correspond to a red-marrow dose of 2.5 Gray. The linear-quadratic model of call survival is employed to transform the resealed duster dose to TCP. Clusters from 20 to 200 {mu}m in radius, and 16 radionuclides of varying decay properties, are included in the study. The salient result is that intermediate-range beta emitters give TCP near 100% for most or all cluster radii examined. For example, I-131 delivers TCP > 99.999% for all cluster sizes. Short-range Auger emitters (e.g., I-125) are found to be ineffectual against the larger clusters (R > 150 {mu}m). The longer-range emitters, e.g., Y-90, are also found to be suboptimal Y-90 generally gives a TCP << 1, but there is a sharp peak (TCP = 75%) near R = 75 {mu}m. No such peak is seen in the corresponding plot of dose vs. R. This work illustrates quantitatively the potential of RIT to deliver a highly tumoricidal dose to blood-borne micrometastases. Further, it indicates which radionuclides may be optimal for this purpose and to what degree the choice is critical. Finally, it demonstrates the value of using tumor control, Instead of dose, in assessing therapeutic effectiveness. The clinical relevance of this work will depend in part upon the tendency of malignant cells to form blood-borne clusters as one step in the metastatic cascade.

• OSTI ID: 197988
• Report Number(s): CONF-940605--
• Journal Information: Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 35; ISSN 0161-5505; ISSN JNMEAQ
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
DIFFERENTIAL EQUATIONS
DOSIMETRY
METASTASES
NEOPLASMS
PERFORMANCE
PROBABILITY
RADIOIMMUNOTHERAPY