Iodine-131-labeled diphosphonates for the palliative treatment of bone metastases--III. Considerations of interaction, binding and absorbed dose.

General considerations about the possible mechanisms of action of rather low dose ionizing radiation with bone metastases and stimulated nerve fibers reveal that only minute amounts of chemicals are produced by direct interaction of energetic electrons. Thus changes of the chemical milieu due to direct interaction must be ruled out in favour of a radiation-induced trigger reaction which may then initiate a cascade of cellular responses. Organ distribution studies of a series of radioiodinated benzylidenediphosphonates with H-, HO- and H2N- in the alpha- and p-position revealed best results for pHO-NH2 (BDP3). The microscopic distribution of 131I-DBP3 in bone tissue was monitored by autoradiography. Elevated uptake in normal (tibia) and neoplastic bone (experimental osteosarcoma) corresponded with the degree of vascularization and formation of new hydroxylapatite. Unlike the uptake in human osteoblastic bone metastases the experimental osteosarcoma of SD-rats accumulated 131I-BDP3 less than normal bone. This was due to the short volume doubling time, the delay of hydroxyl-apatite deposition and the formation of necroses. Theoretical replacement of 131I in iodinated BDP3 with radioisotopes emitting higher energy electrons yielded best bone metastasis/organ ratios for 32P labeled BDP3. The bone metastasis/bone marrow dose ratio by comparison with 131I labeled BDP3 is, however, almost equal. The isotopes 130I and 133I are not suited to the achievement of higher tumor/background doses although they are higher energy beta- -emitters than 131I. Because of their short physical half life and absence of different kinetics in normal and neoplastic bone no dose enhancement in bone metastases can be attained.