technetium-tc-99m-depreotide and Breast-Neoplasms

In vitro assessment of hormone receptor status using a ligand-binding assay or immunohistochemistry in breast cancer patients predicts endocrine responsiveness with an accuracy of only 60%-70%. Assessment of an end product of estrogen receptor stimulation, such as the progesterone receptor, is assumed to provide a measure of functional receptor content and has proven to increase predictive accuracy. In analogy with the estrogen-dependent regulation of somatostatin receptor (SSTR) expression in endocrine-responsive human breast cancer cell lines, efficient antiestrogen treatment in patients may result in a downregulation of SSTR at the cell surface in breast tumors. In vivo imaging of this molecular event by means of sequential (99m)Tc-depreotide scintigraphy could enable selection of breast cancer patients susceptible to endocrine therapy.. Twenty patients with a diagnosis of advanced breast cancer in whom first- or second-line hormonal therapy was going to be initiated were included. Patients underwent sequential (99m)Tc-depreotide scintigraphy before and 3 wk after initiating hormonal treatment. Follow-up data were retrieved from routine clinical evaluation by means of physical examination, imaging (e.g., bone scan, CT, MRI) and blood analysis. Lesion-to-background ratios (L/BGs) were calculated on planar and SPECT images and a change of >25% between the baseline and follow-up scan was considered significant.. At 6 mo after initiation of treatment, 8 patients had stable disease and were considered to be responding to hormonal treatment, whereas 10 patients had progressive disease and were considered to be nonresponders. The positive and negative predictive values of baseline (99m)Tc-depreotide scintigraphy for endocrine responsiveness were 73% (8/11) and 100% (7/7), respectively. Sequential scans were always both positive or both negative. The relative change in (99m)Tc-depreotide uptake between sequential scans significantly differed in responders compared with nonresponders (P= 0.017)-uptake decreased in the first group and increased in the latter. As such, baseline (99m)Tc-depreotide scintigraphy combined with the changes in tracer uptake between the baseline and follow-up scan predicted endocrine responsiveness with an accuracy of 100%.. Sequential (99m)Tc-depreotide scintigraphy could allow for separation of responders and nonresponders immediately or as early as 3 wk after initiation of treatment.

Topics: Aged; Antineoplastic Agents, Hormonal; Breast Neoplasms; Estrogen Receptor Modulators; Female; Humans; Middle Aged; Organotechnetium Compounds; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Somatostatin; Treatment Outcome

Investigating three somatostatin receptor (SSTR)-positive (+) human breast cancer cell lines, Xu et al. found a time- and dose-dependent up- or down-regulation of SSTR2 mRNA expression by 17beta-oestradiol (E(2)) or the anti-oestrogen tamoxifen, respectively, in the two oestrogen receptor-positive (ER+) cell lines but not in the oestrogen receptor-negative (ER-) cell line. This study aimed to confirm the findings of Xu et al. at the protein level by means of western blotting and saturation binding studies using (99m)Tc-depreotide (NeoSpect). The ER+/SSTR+ ZR75-1 and T47D and SSTR+/ER- MDA MB231 breast cancer cell lines were exposed to 1 n M E(2) or a combination of 1 n M E(2) plus 100 n M tamoxifen or ICI 182 780 (Faslodex) for 48 h. Exposed and non-exposed controls were incubated with increasing concentrations of (99m)Tc-depreotide (0.5 n M-15 n M) in the absence and the presence of 20 micro M of octreotide. Scatchard-Rosenthal plots were derived using commercially available software. SSTR subtypes responsible for E(2)-induced changes in (99m)Tc-depreotide binding were identified by means of western blotting. Mean K(d) values for (99m)Tc-depreotide were 13 n M, 7 n M and 4 n M for T47D, ZR75-1 and MDA MB231 cells, respectively. After stimulation with E(2), the ER+ cell line T47D demonstrated a mean increase of 81% ( P<0.05) in (99m)Tc-depreotide binding. Adding the partial agonist tamoxifen and full antagonist ICI 182 780 to E(2) blocked the induced increase in T47D cells, either reducing SSTR expression or restoring it to control levels. ZR75-1 cells stimulated with E(2) showed a mean decrease in (99m)Tc-depreotide binding of 36% as compared to control cells; this difference, however, proved to be not statistically significant. Similarly, B(max) values did not change in ZR75-1 cells exposed to E(2) in combination with an ER antagonist as compared to control cells. Finally, no influence of E(2) on (99m)Tc-depreotide binding was observed in the ER- cell line MDA MB231. Both SSTR2 and SSTR5 were expressed at high levels in T47D cells and ZR75-1 cells. SSTR5 drastically increased in the absence of E(2) and was restored to the original detection level after E(2) treatment. The presented findings support an oestrogen-dependent regulation of SSTR expression in breast cancer cell lines.

Topics: Adult; Aged; Breast Neoplasms; Cell Line, Tumor; Estrogens; Female; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin

The purpose of this study was to determine the potential role of Tc depreotide scintigraphy for the evaluation of bone metastases compared with Tc methylenediphosphonate (MDP) bone scintigraphy and for the prediction of treatment response in breast cancer patients in whom first- or second-line hormonal therapy was to be initiated.. Twelve patients with a diagnosis of advanced breast cancer were included. All patients underwent both a bone scan and a depreotide scan and at least one other conventional imaging procedure, including plain film radiography (n=11), computed tomography (n=6) or magnetic resonance imaging (n=5), for confirmation of metastatic disease. The mean time interval between the bone scan and the depreotide scan was 30.6 days. Follow-up data were retrieved from routine clinical evaluation by means of physical examination, imaging and blood analysis.. On a patient basis we found a sensitivity, specificity and accuracy of, respectively 100%, 50% and 83.3% for the bone scan and 62.5%, 100% and 75% for the depreotide scan in the diagnosis of bone metastasis. In eight patients with available follow-up data two with a positive depreotide scan remained stable and five of six patients with a negative depreotide scan had progressive disease.. In this small series of breast cancer patients Tc depreotide scintigraphy proves less sensitive but more specific as compared to Tc-MDP bone scintigraphy in measuring the extent of bone metastasis. On the other hand Tc depreotide scintigraphy elucidates, non-invasively, tumour characteristics and may be indicative for prognosis and response to hormonal treatment.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Bone Neoplasms; Breast Neoplasms; Female; Hormones; Humans; Male; Middle Aged; Organotechnetium Compounds; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Somatostatin; Technetium Tc 99m Medronate; Treatment Outcome

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Humans; Organotechnetium Compounds; Patient Selection; Predictive Value of Tests; Radionuclide Imaging; Somatostatin; Treatment Outcome

This paper reports on the biodistribution and dosimetry of (99m)Tc-depreotide in patients.. Whole body planar images were acquired 30 minutes, 1, 2, 4, 9, and 24 hours after intravenous injection of 555-740MBq (99m)Tc-depreotide in 5 breast cancer patients. Urine was collected up to 24 hours after injection, allowing for a calculation of renal clearance and an interpretation of whole body clearance. Time activity curves were generated for the thyroid, lungs, liver, spleen, kidneys, colon, thoracic vertebrae/sternum, and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest (ROIs). The Medical Internal Radiation Dose (MIRD) formulation was applied to calculate the absorbed radiation dose for various organs.. The whole body images show most of the activity distributed in the liver, spleen, and kidneys. Nearly all excretion of activity occurred by the renal system, and hepatobiliary excretion was negligible. Elimination of administered activity occurred predominantly through physical decay. The mean cumulative measured urinary excretion at 24 hours postinjection was 14.0% (standard deviation; 11.8%) of the administered activity. The highest absorbed dose was received by the kidneys, thyroid, and spleen. The average effective dose was estimated to be 1.15E-02mSv/MBq (standard deviation; 1.41E-03mSv/MBq).. The biodistribution of (99m)Tc-depreotide demonstrated low lung and myocardial uptake allowing early imaging of the supradiaphragmatic region and this with a dosimetry favorable for clinical whole body and single photon emission computed tomography (SPECT) imaging.

Topics: Breast Neoplasms; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Organotechnetium Compounds; Radiation Dosage; Radiometry; Radionuclide Imaging; Somatostatin; Tissue Distribution

Tc-99m depreotide (NeoSpect) is a radiolabeled somatostatin analog introduced recently for scintigraphic imaging of patients with lung cancer. Eighteen patients were examined 2 to 4 hours after administration of 740 MBq mCi Tc-99m depreotide. In 13 patients (72.2%) bilateral symmetric activity corresponding to the large, deep apocrine sweat glands of the axillae was present. This observation is clinically relevant regardless of its reason or mechanism. It is important to be aware of this reason for activity in the axillae when assessing lymph node involvement not only in patients with lung cancer but also in breast cancer patients using scintigraphy with Tc-99m depreotide.

Topics: Axilla; Breast Neoplasms; Female; Humans; Lung Neoplasms; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Somatostatin; Sweat Glands

Topics: Aged; Breast Neoplasms; Female; Humans; Organotechnetium Compounds; Radiopharmaceuticals; Somatostatin; Tomography, Emission-Computed, Single-Photon