A Monte Carlo simulation model for radiation dose to metastatic skeletal tumor from rhenium-186(Sn)-HEDP.

UNLABELLED: A Monte Carlo model has been developed for simulation of dose delivery to skeletal metastases by the bone surface-seeking radiopharmaceutical 186Re (Sn)-HEDP. METHODS: The model simulates: (1) the heterogeneous small scale geometry of the soft tissue/bone-spicule structure in the lesions as determined by histomorphometric measurements of histologic specimens, (2) the small scale spatial distribution of the radiopharmaceutical on the lesion bone spicule surface as determined by autoradiography, and (3) the 186Re beta and conversion electron decay spectrum and the associated charged particle transport within the modeled geometries. The results are compared with the commonly employed uniform lesion model, which assumes: (1) homogeneous lesion morphology, (2) uniform distribution of radioactivity within the lesion, and (3) complete energy deposition by charged particles within the lesion due to decay of this activity. Gamma and x-ray photons from the 186Re spectrum were assumed to escape from the lesion volume in both models. RESULTS: Results show a significant dependence on the bone volume fraction and hence on the histology of the lesion (lytic, blastic or mixed). The uniform lesion model calculations underestimate the radiation dose to blastic lesions by as much as a factor of 1.8. However, for lytic lesions with low bone volume fractions, both models provide similar dose values. CONCLUSIONS: These new model calculations provide a mechanism for optimizing treatment planning and dose response evaluations of therapeutic bone-seeking radiopharmaceuticals.

Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer.

We used a combination of radioiodine scanning and quantitative radiation dosimetry to evaluate responses to therapeutic irradiation with 131I in 76 patients with thyroid adenocarcinoma. Fifty patients received 131I treatment for ablation of residual thyroid tissue after surgical thyroidectomy, and 26 had 131I treatment for metastatic thyroid cancer. Successful ablation was observed in patients receiving higher radiation doses to the thyroid--about 4.4 times those in patients whose lesions were not ablated--largely because of a longer effective half-life of 131I in residual thyroid tissue in the patients with ablated lesions. Patients with metastases that persisted after 131I therapy tended to have more advanced disease and received significantly lower radiation doses per millicurie of administered 131I than did persons whose lesions responded to treatment. Initial 131I treatment resulting in radiation doses of at least 30,000 rad to thyroid remnants and 8000 rad to metastases was associated with a significant increase in the rate of response to therapy.

Low iodine diet in I-131 ablation of thyroid remnants.

A low-iodine diet was developed for used in decreasing iodine intake and excretion in patients undergoing evaluation with radioactive I-131 for ablation of thyroid remnants as treatment for thyroid cancer. It has been demonstrated to effectively lower iodine excretion to less than 25% of basal values. Preliminary calculations suggest that such iodine depletion may be potentially useful in increasing the radiation dose per mCi of administered activity in I-131 ablative therapy.

A quantitative method to measure human platelet chemotaxis using indium-111-oxine-labeled gel-filtered platelets.

Human blood platelets have been shown to migrate directionally and specifically toward collagen in plasma in vitro. We have developed a new system to monitor this behavior using a linear 7-compartment chamber with 111In-oxine-labeled gel-filtered platelets. The compartments are separated by various Nuclepore and Millipore filter membranes. Radiolabeled platelets suspended in plasma are placed in the central compartment and the other compartments are filled with platelet-free plasma. When collagen is added to an end compartment, platelets migrate toward that end. The degree of this directed movement or chemotaxis can be measured by counting the radioactivity of the contents of each compartment and then comparing the counts from radiolabeled platelets that have moved to the end that holds the chemotactic inducer with those that have randomly migrated to the opposite end, containing only plasma. This assay system allows quantitative comparisons between the chemotaxis-inducing abilities of different substances and permits the study of soluble materials. Experiments to determine the optimal conditions for the procedure are reported, and the advantages of this new method for the investigation of platelet chemotaxis and the identification of chemotaxins are discussed.

Stability of immunologic activity of human prostatic acid phosphatase in serum.

The stability of the immunologic activity of human serum prostatic acid phosphatase (iPAP;EC 3.1.3.2) under various storage conditions was evaluated. Although more stable than the enzymic activity of serum PAP, serum iPAP was inactivated rapidly at room temperature at neutral and especially at alkaline pH. Purified iPAP in a phosphate buffer (pH 7.5) was stable for at least three days at room temperature but showed instability similar to that of serum iPAP when added to heat-treated serum (30 min at 56 degrees C, pH 8.3). Addition of a protease inhibitor, a sulfhydryl agent, or a chelating agent failed to preserve iPAP. Acidification of serum with an acetate buffer (5 mol/L, pH 5.0), 20 microliters/mL of serum, protected but could not restore serum iPAP activity. When stored at 24 degrees C, serum iPAP was most stable at pH 6.5. Acidification had little effect on PAP values by radioimmunoassay, iPAP values from acidified and unacidified serum samples being essentially the same. We recommend that blood samples drawn for PAP immunoassays be kept at 4 degrees C and that serum samples be separated and acidified as soon as practical. For long-term storage, acidified serum samples should be kept in small aliquots at -20 or -70 degrees C.