germanium and Prostatic-Neoplasms

Neuroendocrine differentiation of prostate cancer (PCa) is a relatively frequent event, generally understudied, that carries important prognostic information. It is the most frequently observed during the advanced stages of disease, when PCa has lost its sensitivity to androgen deprivation therapy or to chemotherapy, moderate to diffuse bone metastatic spread dominates the imaging scenario and it is responsible for painful clinical symptomatology. However, evidences indicate that neuroendocrine differentiation is a progressive phenomenon that starts at the very early part of the pathogenesis of cancer transformation contributing to it. Neuroendocrine tumor phenotypes have reduced capability to secrete the prostate specific antigen (PSA) and therefore PSA does not represent a reliable marker to follow-up neuroendocrine differentiation. Tumor progression may be monitored by measuring plasma concentration of neuroendocrine tumor markers, primarily chromogranin A and neuron-specific enolase. Several nuclear medicine tracers are available for studying different biochemical properties of tumor cells with neuroendocrine differentiation. Single photon computed emission tomography (SPECT) with [111In-diethylenetriaminepentaacetic acid] ([111In-DTPA0])- octreotide (Octreoscan) has been extensively used in the past. However, the development of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), which in comparison to DTPA allows higher affinity bindings for beta-emitting radionuclides and for somatostatin (SST) analogues, and the increased availability of the Germanium-68/Gallium-68 (68Ge/68Ga)-generator, which enables positron emission tomography/computed tomography (PET/CT) imaging, have allowed the synthesis of several PET tracers for different SST receptors. The receptor of the bombesin/ gastrin releasing peptide (GRP), which is overexpressed in PCa with neuroendocrine differentiation, also represents an innovative research field with diagnostic and therapeutic applications through, respectively, positron and beta emitters. At the moment, however, we observe some discrepancy between the high number of preclinical studies and the small number of clinical studies, most likely related to competing and, at the moment, more effective radiopharmaceuticals for imaging and for radiometabolic therapy, such PET/CT with radiolabeled choline and prostate-specific membrane antigene (PSMA)-ligands, the latter being labeled either with 68Ga for imagin

Topics: Bombesin; Gallium Radioisotopes; Gastrin-Releasing Peptide; Germanium; Heterocyclic Compounds, 1-Ring; Humans; Male; Neuroendocrine Tumors; Pentetic Acid; Phenotype; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radioisotopes; Radiopharmaceuticals; Somatostatin; Tomography, Emission-Computed, Single-Photon

The assessment of dose and ultimately the health risk from intakes of radioactive materials begins with estimating the amount actually taken into the body. An accurate estimate provides the basis to best assess the distribution in the body, the resulting dose and ultimately the health risk. This study continues the time-honoured practice of evaluating the accuracy of results obtained using in vivo measurement methods and techniques. Results from the radiochemical analyses of the (241)Am activity content of tissues and organs from four donors to the United States Transuranium and Uranium Registries (USTUR) were compared with the results from direct measurements of radioactive material in the body performed in vivo and post-mortem. Two were whole-body donations and two were partial-body donations. The (241)Am lung activity estimates ranged from 1 to 30 Bq in the four cases. The (241)Am activity in the lungs determined from the direct measurements were within 40% of the radiochemistry results in three cases and within a factor of 2 for the other case. However, in one case the post-mortem direct measurement estimate was a factor of 10 higher than the radiochemistry result for lung activity, most probably due to underestimating the skeletal contribution to the measured count rate over the lungs. The direct measurement estimates of liver activity ranged from 2 to 60 Bq and were consistently lower than the radiochemistry results. The skeleton was the organ with the highest deposition of (241)Am activity in all four cases. The skeletal activity estimates ranged from 30 to 300 Bq. The skeletal activity obtained from measurements over the forehead were within 20% of the radiochemistry results in three cases and differed by 78% in the other case. The results from this study suggest that the measurement methods, data analysis methods and calibration techniques used at the In Vivo Radiobioassay and Research Facility can be used to quantify the activity in the lungs, skeleton and liver when (241)Am activity is present in all three organs. The adjustment method used to account for the contribution from activity in other organs improved the agreement between the direct measurement results and the radiochemistry results for activity in the lungs and skeleton. The method appeared to overestimate the contribution from the other organs to the liver activity measurements, although the low activity levels complicated the analysis. The unadjusted liver activity estimates from t

Topics: Acute Disease; Adult; Aged, 80 and over; Americium; Autopsy; Body Burden; Bone and Bones; Cadaver; Germanium; Humans; Liver; Lung; Lung Neoplasms; Male; Mitral Valve; Myocardial Infarction; Plutonium; Prostatic Neoplasms; Radiochemistry; Tissue Distribution; Tissue Donors; Young Adult

A series of Ge132 derivatives have shown enhanced antitumor activity. Previous studies suggest that DNA can be their primary target. Here we show direct evidence that two newly synthesized Ge132 derivatives can intercalate into DNA. Unexpected methyl substitution effect of the novel derivatives on DNA sequence selectivity and cytotoxicity was observed.

Topics: Animals; Antineoplastic Agents; Cattle; Cell Cycle; Cell Proliferation; DNA; Drug Screening Assays, Antitumor; Germanium; Humans; Inhibitory Concentration 50; Intercalating Agents; Male; Organometallic Compounds; Propionates; Prostatic Neoplasms; Quinolines; Tumor Cells, Cultured

Topics: Aged; Antineoplastic Agents; Drug Evaluation; Germanium; Humans; Male; Middle Aged; Neoplasm Metastasis; Organometallic Compounds; Prostatic Neoplasms; Spiro Compounds

A phase II study of spirogermanium was conducted in a series of 15 patients with metastatic prostatic carcinoma. All the patients have previously received multiple hormonal therapies. The drug was administered at the dose of 200 mg/m2 by a continuous infusion for five days, and 120 mg/m2, three times a week subsequently. The side effects were mainly neurological toxicity and phlebitis at the injection points which were dose and schedule dependent. Only one partial response for two months was noted in this series. Thus, spirogermanium seems to have a limited value in patients with prostatic cancer.

Topics: Aged; Antineoplastic Agents; Drug Evaluation; Germanium; Humans; Male; Middle Aged; Neoplasm Metastasis; Organometallic Compounds; Prostatic Neoplasms; Spiro Compounds