Extent of particulate marker (samarium, lanthanum and cerium) movement from one digesta particle to another.
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Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. We applied high-activity Sm-153-EDTMP therapy within a multimodal therapy concept to improve local control of an unresectable osteosarcoma with poor response to initial polychemotherapy. A 21-year-old woman with an extended, unresectable pelvic osteosarcoma and multiple pulmonary metastases was treated with high-activity of Sm-153- EDTMP (150 MBq/kg BW, total 8.1 GBq). Afterwards external radiotherapy of the primary tumor site was performed and polychemotherapy was continued, followed by autologous peripheral blood stem cell reinfusion. Within 48 h after Sm-153-EDTMP application the patient had complete pain relief. After three weeks the response was documented by 3-phase Tc-99m-MDP bone scintigraphy (primary tumor and metastases: decreased tracer uptake), whole-body F-18-FDG-PET (primary tumor and metastases: diminution of glucose metabolism) and thoracic CT (metastases: reduction of size). The present case warrants further evaluation of feasibility and efficacy of this multimodal therapy combination of high-activity Sm-153-EDTMP therapy, external radiation, polychemotherapy and stem cell support for unresectable osteosarcomas.
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A study was undertaken to determine the degree of acute bone marrow and vital organs injury sustained when dogs were administered doses of 153Sm-EDTMP calculated to irradiate an acute bone lesion arising from cancer metastasis to a dose considered palliative or even therapeutic (20-160 Gy). The study revealed significant (p less than 0.05) temporary depression of the bone marrow in all doses in the therapeutic (greater than 40 Gy) range. Palliative (20 Gy) doses caused significant leukocyte depression but insignificant (p greater than 0.05) depression of platelet and packed cell volumes when compared to control animals. A mild transient rise in the levels of serum alkaline phosphatase occurred immediately following radioisotope administration. All hematologic parameters had returned to normal by six weeks after the last injection of radioisotope. The study indicates potential for this compound as a safe, therapeutic radiopharmaceutical for treatment of cancer bone metastasis.
Forty dogs with spontaneous skeletal neoplasia were treated with 153Sm-EDTMP (ethylenediaminetetramethylene phosphonic acid). Both primary and metastatic lesions were treated. Two treatment regimes, a single (37 MBq (1.0 mCi)/kg dose or two 37 MBq (1.0 mCi)/kg doses separated by 1 wk) were tested. Response to treatment was varied. Large lesions with minimal tumor bone formation responded poorly, while primary lesions with substantial ossification usually exhibited a transient response. Small lesions with minimal lysis, metastatic lesions, and axial skeleton lesions generally responded well. The major adverse side effects of treatment were platelet and white blood cell count depression below baseline values for up to 4 wk (p less than 0.05). Minor depression of packed cell volume and transient elevation of serum alkaline phosphatase were also noted (p less than 0.05). No significant differences (p greater than 0.05) between the two treatment groups, either in treatment effect or undesirable side effects, were detected.
The labeling of a monoclonal antibody K-1-21 with 153Sm has been investigated using the bifunctional chelate cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride. Labeling efficiencies greater than 60% were obtained using high specific activity [153Sm]chloride and a cDTPAa:MAb conjugation ratio of 20:1. The resultant labeled antibody had a s.a. greater than 150 MBq.mg-1 and a % retained immunoreactivity greater than 90%. Imaging and biodistribution studies in a rat model demonstrated that specific uptake of 153Sm-K-1-21 into s.c. implants of the target antigen could be clearly detected in scintigrams at 6 days p.i. The specific uptake (1.90 +/- 0.45% ID/g, 19.95 +/- 2.20 Implant:Blood ratio) compared favorably to 131I- and 111In-labeled K-1-21 (2.52 +/- 0.20 and 3.33 +/- 0.20% ID/g, 7.69 +/- 0.45 and 10.10 +/- 0.60 I:B, respectively). Labeling of MAbs with 153Sm for combined scintigraphy/therapy is feasible at clinically appropriate specific activities using cDTPAa, with the resultant conjugates retaining immunoreactivity and in vivo antigen localization.
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A series of stable complexes of 153Sm has been produced using multidentate acetate and phosphonate ligands. Biodistribution studies in unanesthetized rats showed varying degrees of bone and soft-tissue uptake for these complexes. Of the complexes studied, [153Sm] ethylenediaminetetramethylenephosphonate (EDTMP) showed the best combination of high bone uptake, low nonosseous uptake, and rapid blood clearance which warranted its further investigation in rabbits. Rabbit studies confirmed the [153Sm]EDTMP results obtained in rats. Blood clearance in rabbits was found to be more rapid than [99mTc] methylene diphosphonate (MDP). Scintigraphic images were virtually indistinguishable from [99mTc]MDP images. Lesion/normal bone ratios were determined from digitized images obtained using a drill hole model and found to be approximately 17:1. Based on these excellent biodistribution characteristics, [153Sm] EDTMP could be therapeutically useful in treating metastatic bone cancer.
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