Mechanisms Of Radiopharmaceutical Localization

Bone metastases may be radiographically osteolytic, reflecting the loss of adjacent bone, or osteoblastic when there is more new bone produced than is lost. The radiographic appearance of a bone metastasis is therefore the net result of the balance of osteoclast activity, direct resorption of bone caused by tumor-secreted factors, and production of new reactive or "woven" bone by adjacent osteoblasts. In the great majority of these metastases there is an osteoblastic component. This leads to localization of these radiopharmaceuticals listed in the table, which bind rather selectively to reactive bone [as does the bone scanning agent technetium-99m methylene diphosphonate (MDP)] because of specific interactions with the dominant bone mineral, hydroxyapatite. In reactive bone surrounding osteoblastic metastases there is a large surface area of amorphous hydroxyapatite which appears prior to crystallization, leading to an excess of bone-seeking radiopharmaceutical deposition relative to normal bone, in ratios ranging between 2 and 15:1, although the usual abnormal-to-normal bone ratio is in the range of 3 to 5:1. Specific mechanisms of deposition will be discussed with each radiopharmaceutical, but all require adequate blood flow to the metastasis. It is an as yet unexplained fact that many, if not all, of these radiopharma-ceuticals are retained longer in woven or reactive than in normal bone, further enhancing the abnormal-to-normal bone ratios, and, presumably, their therapeutic effectiveness. These radiotracers all have a significant element of renal excretion; Sr-89 and P-32 will also appear in the feces to some extent. None of the organs of either system (genitourinary, gastrointestinal) receive a significant radiation dose if the patient is well hydrated and defecates daily. The marrow always receives a biologically significant dose, which may lead to mild to moderate, reversible myelosuppression. No other organ receives a significant radiation dose. Whole-body retention of these compounds ranges from about 30% to 40% in a nearly normal skeleton to close to 90% in the presence of widespread metastatic disease.

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