ABSTRACT: The etiology of osteonecrosis of the jaw is poorly understood, but preferential mandibular uptake of intravenous bisphosphonates (IVBPs) has been implicated. We examined this association within a prospective study assessing the effect of IVBPs on radionuclide bone scanning.
Women with at least 3 osseous breast metastases on bone scanning and previous IVBP use within 8 weeks were eligible for the present study. After the first clinically indicated bone scan, the patients received zoledronic acid within 72 hours and underwent a second bone scan within another 72 hours. The regions of interest on the bone scan were read in triplicate, and the mean count per pixel was calculated for the mandible (C(M)), left femur (C(FL)), right femur (C(FR)), and thigh (C(B)). The mandibular bone turnover (MBT) was quantified as the ratio of (C(M) - C(B))/(C(F) - C(B)), where C(F) = (C(FL) + C(FR)/2). The MBT was compared before and after IVBP use.
A total of 10 patients were enrolled (median age 51 years, range 40 to 71); none had known osteonecrosis of the jaw. Of the 10 patients, 8 had paired bone scans available for analysis. The previous zoledronic acid exposure was 48.6 mg (range 24 to 148) for a median of 13 months (range 6 to 35). The baseline mean MBT ratio was 2.33 (range 0.88 to 4.22). After IVBP administration, the mean MBT ratio was statistically unchanged at 2.23 (range 1.05 to 3.09). The MBT had declined in 4 patients and increased in 4. Only 1 patient had had an MBT of less than 1.0 before IVBP use, and no patient had an MBT ratio of less than 1.0 after IVBP use.
The mandibular region appears to be a site of increased uptake of technetium-99m bound to methylene diphosphonate-technetium. Acute changes in bisphosphonate binding in the mandible were not observed in our patients receiving chronic IVBP therapy.
Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 11/2010; 69(1):114-9. · 1.58 Impact Factor
ABSTRACT: Early studies of patients with castration-resistant metastatic prostate cancer (CRMPC) suggest that chemotherapy administered with a dose of a bone-seeking radiopharmaceutical is superior to chemotherapy alone. To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 ((153)Sm) lexidronam.
Men with progressive CRMPC were eligible. Cohorts of three to six patients were defined by dose escalations as follows: docetaxel 65, 70, 75, 75, 75 mg/m(2) and (153)Sm ethylenediaminetetramethylenephosphonate (EDTMP) 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle lasted a minimum of 6 (cohorts 1 through 5) or 9 (cohort 6) weeks. Docetaxel was administered on days 1 and 22 (and day 43 for cohort 6), and (153)Sm-EDTMP was administered on day -1 to 1 of each cycle. Patients with acceptable hematologic toxicities were eligible to receive additional cycles until progression.
Twenty-eight men were treated in six cohorts. Maximum-tolerated dose was not reached, because full doses of both agents were well tolerated, even using an every-6-week dosing schedule of (153)Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9 (153)Sm-EDTMP doses (range, one to six doses). Fifteen patients demonstrated a more than 50% decline in prostate-specific antigen. Treatment significantly reduced indices of bone deposition and resorption.
Docetaxel and (153)Sm-EDTMP can be combined safely at full doses over repeated cycles. Responses were seen in the small group of patients with taxane-resistant disease tested. The optimal phase II doses for patients with taxane-naïve disease may differ from those optimal for patients with taxane-resistant disease.
Journal of Clinical Oncology 05/2009; 27(15):2436-42. · 18.37 Impact Factor
ABSTRACT: The in vitro and in vivo behavior of the radiolabeled monoclonal antibody MORAb-003 was investigated as a prelude to a clinical trial.
The cellular retention of 111In- and 131I-labeled MORAb-003 was investigated using IGROV1 and SW620 cells. Biodistribution studies in tumor-bearing mice were performed with the more favorable agent.
Five 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA) molecules were conjugated to MORAb-003 with no apparent loss of immunoreactivity. Radiolabeled MORAb-003 had a high affinity for the folate receptor alpha (FRA) expressed by both IGROV1 and SW620 cells and was found to bind to around 8 x 10(5) and 7 x 10(5) sites/cell, respectively. Both cancer cell lines were found to internalize both 131I- and 111In-labeled MORAb-003, but 111In was retained and 131I was released as iodide. In athymic mice, 111In-DOTA-MORAb-003 was cleared from the blood with a single exponential biological clearance rate of 110 h. The uptake in SW620 tumors was 32+/-5%ID/g after 4 days. The clearance rate of activity from normal organs such as liver, kidney and spleen was similar to the blood clearance and was 5.36%ID/g, 4.03%ID/g and 4.36%ID/g at 1 day postinjection and 2.14%ID/g, 1.65%ID/g and 3.74%ID/g after 8 days, respectively. In a pilot clinical study, the biodistribution and tumor targeting of 111In-MORAb-003 was assessed in three patients undergoing treatment with cold MORAb-003.
MORAb-003 is an attractive antibody for radioimmunoscintigraphy and possibly radioimmunotherapy of FRA-expressing cancers in addition to its potential direct therapeutic effects.
Nuclear Medicine and Biology 05/2008; 35(3):343-51. · 3.02 Impact Factor