phosphorus-radioisotopes and Pain--Intractable

Bone pain is a common complication for terminal patients with bone metastases from prostate, lung, breast, and other malignancies. A multidisciplinary approach in treating bone pain is generally required, 1 which includes a combination of analgesic drug therapy, radiation therapy, hormonal therapy, and chemotherapy. Over the years, treatment of bone pain using bone-seeking radiopharmaceuticals has been explored extensively. Pharmaceuticals labeled with energetic 1-particle emitters such as 32p, 89Sr, 153Sm, and 186Re, in addition to the low-energy electron emitter 117mSn, have been studied for this purpose. Bone-marrow toxicity as a consequence of chronic irradiation by the energetic , particles is a general problem associated with this form of treatment. It is therefore desirable to identify radiochemicals that minimize the dose to the bone marrow and at the same time deliver therapeutic doses to the bone.. New S values (mean absorbed dose per unit cumulated activity) for target regions of human bone and marrow were used to ascertain the capacity of various radiochemicals to deliver a high bone dose while minimizing the marrow dose. The relative dosimetric advantage of a given radiopharmaceutical compared with a reference radiochemical was quantitated as a dosimetric relative advantage factor (RAF). Several radionuclides that emit energetic 1 particles (32p, 89Sr, 153Sm, 186Re, and 177Lu) and radionuclides that emit low-energy electrons or beta particles (169Er, 117mSn, and 33p) were evaluated. For these calculations, ratios of the cumulated activity in the bone relative to cumulated activity in the marrow alpha equal to 10 and 100 were used.. When the radiopharmaceutical was assumed to be uniformly distributed in the endosteum and alpha was taken as 100 for both the reference and test radiochemicals, the RAF values compared with the reference radionuclide 32p were 1.0, 1.2, 1.4, 1.6, 1.7, 1.9, and 2.0 for 89Sr, 186Re, 153Sm, 177Lu, 169Er, 117mSn, and 33P, respectively. In contrast, when the radiopharmaceutical is assumed to be uniformly distributed in the bone volume, the RAF values for these 7 radionuclides were 1.1, 1.5, 2.4, 3.2, 4.5, 5.1, and 6.5, respectively.. These results suggest that low-energy electron emitters such as 117mSn and 33P are more likely to deliver a therapeutic dose to the bone while sparing the bone marrow than are energetic beta emitters such as 32p and 89Sr. Therefore, radiochemicals tagged with low-energy electron or beta emitters are the radiopharmaceuticals of choice for treatment of painful metastatic disease in bone.

Topics: Bone Marrow; Bone Neoplasms; Humans; Pain, Intractable; Palliative Care; Phosphorus Radioisotopes; Radioisotopes; Radiopharmaceuticals; Radiotherapy Dosage; Tin

Topics: Analgesics, Non-Narcotic; Animals; Bone Neoplasms; Humans; Organometallic Compounds; Organophosphorus Compounds; Pain, Intractable; Palliative Care; Phosphorus Radioisotopes; Radioisotopes; Samarium; Strontium; Strontium Radioisotopes

The short range tissue destruction of beta-emitting radioisotopes can be utilized in painful metastatic disease of the skeleton by employing a radionuclide that is specifically metabolized in or adjacent to these lesions. Sodium phosphate P 32 has been used for this purpose for the past 25 yr. It uptake in skeletal tumor and in osteoblastic new bone adjacent to tumor can be markedly increased by pharmacologic stimulation using androgenic steroids, or during rebound deposition after a course of parathyroid hormone. Although efficacy in terms of subjective pain relief is high, more objective signs of success are often lacking, and survival, while more confortable, is not prolonged. Marrow depression is the most significant side effect. A beta-emitting, bone-seeking isotope, 89Sr, may have a better therapeutic/toxic ratio, and should receive further trial. Radiation-induced necrosis has also been applied, though more hesitantly, to the proliferative, destructive, but nonmalignant synovium in rheumatoid disease. Here, a number of colloidal preparations, most commonly 198Au, have been employed. Again, relief of symptoms, particularly recurrent joint effusions, is quite high, although the basic disease process is not reversed. The major hazard here appears to be leakage of material to regional lymph nodes, resulting in irradiation of circulating lymphocytes. Although chromosomal damage can be detected when such cells are then cultured, the actual consequences of this, if any, are not presently known. Both shorter-lived (165Dy) and longer-lived (32P) larger-size colloids are being evaluated, which may prove safer in this regard than 198Au.

Topics: Bone Marrow; Bone Neoplasms; Gold Radioisotopes; Humans; Joint Diseases; Neoplasm Metastasis; Pain, Intractable; Palliative Care; Phosphorus Radioisotopes; Radiation Dosage; Radioisotopes; Strontium Radioisotopes; Synovial Membrane

Topics: Adult; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Neoplasm Metastasis; Pain, Intractable; Palliative Care; Phosphorus Radioisotopes; Prostatic Neoplasms; Testosterone

Thirty-three patients with intractable pain caused by diffuse osteoblastic metastases from carcinoma of the prostate were treated with phosphorus-32 (32P) therapy either androgen priming, parathormone rebound, or a combination of both priming methods. Significant response to pain was achieved in 12 of 19 patients receiving testosterone-potentiated therapy, 0 of 5 patients treated with parathormone alone, and 6 of 9 patients receiving a combination of both priming modalities. It is concluded that androgen priming alone is the simplest and most effective method to be used when 32P therapy is being considered for palliative control of pain in patients with carcinoma of prostate.

Topics: Aged; Bone Neoplasms; Drug Therapy, Combination; Humans; Male; Middle Aged; Neoplasm Metastasis; Pain, Intractable; Palliative Care; Parathyroid Hormone; Phosphorus Radioisotopes; Prostatic Neoplasms; Testosterone

Topics: Aged; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Pain, Intractable; Phosphorus Radioisotopes; Prostatic Neoplasms; Testosterone

Topics: Blood Platelets; Bone Neoplasms; Breast Neoplasms; Calcium; Female; Follow-Up Studies; Humans; Male; Neoplasm Metastasis; Pain, Intractable; Palliative Care; Parathyroid Hormone; Phosphorus; Phosphorus Radioisotopes; Prostatic Neoplasms; Testosterone