Five years after single intravenous injection of a mixture of 239Pu and 90Sr to semifine-wool sheep (7.4 kBq/kg + 185 kBq/kg) the iodine-fixing and hormone secreting functions of the thyroid gland were inhibited; where 90Sr alone was injected in the above dose inhibited was the hormone-secreting function only. Since 239Pu alone did not cause such alterations, the observed remote effect was attributed to the effect of the incorporated 90Sr.

Strontium-89 has a physical half-life of 50.5 days. It undergoes beta-minus decay with a beta emission of 1.463 MeV. Maximum range is about 8mm, therefore the greatest radiation dose is to the cortical and trabecular bone, with less to the radiosensitive marrow and minimal irradiation to adjacent soft tissues. The agent follows the biochemical pathways of calcium in the body (it is a calcium analog).

Following intravenous injection of the agent it clears rapidly from the blood, with more than 50% of the injected dose localizing to the skeleton. Preferential bone uptake occurs at sites of active osteoblastic activity. The biologic half-life of Sr-89 in normal bone is about 14 days, but the half-life in osseous mets can be over 50 days due to preferential retention in these sites [Nuclear Medicine Annual, 1992, p.74]. This allows a large therapeutic gain to occur in terms of total radiation dose delivered to tumor and non-tumor bearing bone.

Excretion is primarily renal/urinary (2/3) and is greatest during first 2 days after administration. Some fecal excretion also occurs (1/3). Levels of Strontium in the urine for 7 to 10 days after treatment require routine personal hygiene measures for urine disposal, and advice to incontinent patients. No special precautions are necessary. Since there are no gamma emissions, the patient does not pose a radiation hazard. Cremation and postmortem examinations can be performed without risk to the technician.

Sr-89 can provide adjunctive therapy for metastatic bone pain. The goals of this treatment are to improve quality of life and possibly survival. About 50% of bone mets are due to breast, prostate or lung cancer. Approximately 80% of bone mets are found in the axial skeleton. The incidence of bone mets varies with the stage of disease:

Breast cancer: Stage I: 2%; Stage II: 6%; Stage III: 15%; and at time of first recurrence: 30%.

Prostate cancer: Stage A: 5-10%; Stage B: 10-15%; and Stage C: 20-30%. Once patients with advanced prostate cancer fail hormonal therapy, the outlook is poor with a median survival of about 9 months. In patients with multiple bone lesions, XRT cannot be used effectively. The major clinical problem in these patients is pain relief.

For bone pain palliation an administered dose of 4mCi (or 40-60uCi/kg body weight [1.5MBq/kg]) is used. No dose response relationship has yet been demonstrated. The absorbed dose to the bone marrow is about 74 rad/mCi.

Between 65-75% of patients with painful bone mets report pain relief following Sr-89 treatment, although complete pain relief is achieved in less than 20% of patients. Patients may note transient increased bone pain within the first 36 to 72 hours post-treatment. This is typically mild, self-limited, and controlled with analgesics. The onset of pain relief is generally within 7 to 21 days, with a mean duration of relief of about 6 months. Re-treatment can be performed at intervals of not less than 90 days (3 months). Re-treatment with Sr-89 within 6 weeks after the first dose has not been shown to further improve pain relief. This may be related to the long residence time of Sr-89 in metastatic lesions which interferes with subsequent tracer accumulation. Frequent therapies can also be complicated by greater marrow toxicity [Nuclear Medicine Annual 1992,p.79-80]. The more extensive the degree of skeletal metastases, the more likely the patient will not experience complete pain relief- this may be related to dilution of the tracer effect associated with diffuse uptake [Atlanta Course, 94]. Overall, Sr-89 appears to have results similar to local XRT for palliation of pain [Bolger, Sem Onc, 20: 32, 1993], although 2 to 3 weeks are typically required prior to the onset of clinical improvement and XRT achieves pain control more quickly.

Recent combined Sr-89 and external XRT studies demonstrate complete pain relief in 60% of patients [JNM Technology, Sept. 93, p.134]. Adjunctive XRT is also associated with a decreased incidence of recurrent pain at the initial site, as well as decreased development of new pain sites [Int. J Rad Onc Bio Phys 93, 225:805-12; Cancer Supplement, Dec. 1,1993, Vol. 72, No 11: 3433-35].

There is currently no objective evidence of tumor regression or correlation between improved bone scan and improved pain control following Sr-89 therapy. Sr-89 therapy has not been shown to affect patient survival- although PSA and acid phosphatase levels have been shown to decrease in prostate cancer patients following therapy.