Direction modulated brachytherapy (DMBT) for treatment of cervical cancer: A planning study with 192 Ir, 60 Co, and 169 Yb HDR sources.

PURPOSE: To evaluate plan quality of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator using 192 Ir, 60 Co, and 169 Yb HDR brachytherapy sources, for various cervical cancer high-risk clinical target volumes (CTVHR ). MATERIALS AND METHODS: The novel DMBT tandem applicator has six peripheral grooves of 1.3-mm diameter along a 5.4-mm thick nonmagnetic tungsten alloy rod. Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of the 192 Ir, 60 Co, and 169 Yb HDR sources in a water phantom against the literature data. 45 clinical cases that were treated using conventional tandem-and-ring applicators with 192 Ir source (192 Ir-T&R) were selected consecutively from intErnational MRI-guided BRAchytherapy in CErvical cancer (EMBRACE) trial. Then, for each clinical case, 3D dose distribution of each source inside the DMBT and conventional applicators were calculated and imported onto an in-house developed inverse planning optimization code to generate optimal plans. All plans generated by the DMBT tandem-and-ring (DMBT T&R) from all three sources were compared to the respective 192 Ir-T&R plans. For consistency, all plans were normalized to the same CTVHR D90 achieved in clinical plans. The D2 cm3 for organs at risk (OAR) such as bladder, rectum, and sigmoid, and D90, D98, D10, V100, and V200 for CTVHR were calculated. RESULTS: In general, plan quality significantly improved when a conventional tandem (Con.T) is replaced with the DMBT tandem. The target coverage metrics were similar across 192 Ir-T&R and DMBT T&R plans with all three sources (P > 0.093). 60 Co-DMBT T&R generated greater hot spots and less dose homogeneity in the target volumes compared with the 192 Ir- and 169 Yb-DMBT T&R plans. Mean OAR doses in the DMBT T&R plans were significantly smaller (P < 0.0084) than the 192 Ir-T&R plans. Mean bladder D2 cm3 was reduced by 4.07%, 4.15%, and 5.13%, for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. Mean rectum (sigmoid) D2 cm3 was reduced by 3.17% (3.63%), 2.57% (3.96%), and 4.65% (4.34%) for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. The DMBT T&R plans with the 169 Yb source generally resulted in the greatest OAR sparing when the CTVHR were larger and irregular in shape, while for smaller and regularly shaped CTVHR (<30 cm3 ), OAR sparing between the sources were comparable. CONCLUSIONS: The DMBT tandem provides a promising alternative to the Con.T design with significant improvement in the plan quality for various target volumes. The DMBT T&R plans generated with the three sources of varying energies generated superior plans compared to the conventional T&R applicators. Plans generated with the 169 Yb-DMBT T&R produced best results for larger and irregularly shaped CTVHR in terms of OAR sparing. Thus, this study suggests that the combination of the DMBT tandem applicator with varying energy sources can work synergistically to generate improved plans for cervical cancer brachytherapy.

[Research of biocompatibility of nanoparticles with fluorescent domen Er/Yb in the neutrophilic granulocytes system].

Fluorescent tags are extensively used for the diagnostic, labeling and marking in vivo and in vitro systems. In this study, fluorescent nanoparticles with Er/Yb lightning center were tested on neutrophilic granulocytes. The main purpose was to idenfity possible toxic effect. The negative impact of fluorophores on the metabolism of neutrophilic and their enzyme systems, on the receptor-mediated cell responses and on the rigidity of cell membranes was shown. The viability of neutrophils (estimated with the use of propidium iodide) after 2 hours of incubation with the fluorescent nanoparticles in concentrations of 10(-4) and 10(-3) mM was 27.0 +/- 6.6 and 19.07 +/- 3.34 %, respectively.

Ytterbium-169: a promising new radionuclide for intravascular brachytherapy.

PURPOSE: To explore the feasibility of 169Yb (gamma, 93 keV) as a new radionuclide for intravascular brachytherapy (IVBT) in terms of dose distribution, penetration power, and radiation safety features as compared with 125I and 192Ir. METHODS: The dose distributions for catheter-based sources, 169Yb, 125I, and 192Ir, in homogeneous water and in the presence of calcium and a steel stent have been determined and compared using the Monte Carlo method (MCNP4B2 code). The dose rates of the sources were evaluated from 0.02 to 100 cm. RESULTS: In the short distance range (0.02

Phase I study of 90Y-labeled B72.3 intraperitoneal administration in patients with ovarian cancer: effect of dose and EDTA coadministration on pharmacokinetics and toxicity.

The tumor-associated glycoprotein 72 (TAG-72) antigen is present on a high percentage of tumor types including ovarian carcinomas. Antibody B72.3 is a murine monoclonal recognizing the surface domain of the TAG-72 antigen and has been widely used in human clinical trials. After our initial encouraging studies (M. G. Rosenblum et al., J. Natl. Cancer Inst., 83: 1629-1636, 1991) of tissue disposition, metabolism, and pharmacokinetics in 9 patients with ovarian cancer, we designed an escalating dose, multi-arm Phase I study of 90Y-labeled B72.3 i.p. administration. In the first arm of the study, patients (3 pts/dose level) received an i.p. infusion of either 2 or 10 mg of B72.3 labeled with either 1, 10, 15, or 25 mCi of 90Y. Pharmacokinetic studies demonstrated that concentrations of 90Y-labeled B72.3 persist in peritoneal fluid with half-lives >24 h after i.p. administration. In addition, 90Y-labeled B72.3 was absorbed rapidly into the plasma with peak levels achieved within 48 h, and levels declined slowly thereafter. Cumulative urinary excretion of the 90Y label was 10-20% of the administered dose which suggests significant whole-body retention of the radiolabel. Biopsy specimens of bone and marrow obtained at 72 h after administration demonstrated significant content of the label in bone (0.015% of the dose/g) with relatively little in marrow (0.005% of the dose/g). The maximal tolerated dose was determined to be 10 mCi because of hematological toxicity and platelet suppression. This typically occurred on the 29th day after administration and was thought to be a consequence of the irradiation of the marrow from the bony deposition of the radiolabel. In an effort to suppress the bone uptake of 90Y, patients were treated with a continuous i.v. infusion of EDTA (25 mg/kg/12 h x 6) infused immediately before i.p. administration of the radiolabeled antibody. Patients (3 pts/dose level) were treated with doses of 10, 15, 20, 25, 30, 35, 40, or 45 mCi of 90Y-labeled B72.3 for a total of 38 patients. EDTA administration resulted in significant myeloprotection, which allowed escalation to the maximal tolerated dose of 40 mCi. Dose-limiting toxicity was thrombocytopenia and neutropenia. Studies of plasma and peritoneal fluid pharmacokinetics demonstrate no changes compared with patients without EDTA pretreatment. Cumulative urinary excretion of the radiolabel was not increased in patients pretreated with EDTA compared with the untreated group. However, analysis of biopsy specimens of bone and marrow demonstrated that bone and marrow content of the 90Y label was 15-fold lower (<0.001% injected dose/g) than a companion group without EDTA. Four responses were noted in patients who received 15-30 mCi of 90Y-labeled B72.3 with response durations of 1-12 months. These results demonstrate the myeloprotective ability of EDTA, which allows safe i.p. administration of higher doses of 90Y-labeled B72.3 and, therefore, clearly warrant an expanded Phase II trial in patients with minimal residual disease after standard chemotherapy or for the palliation of refractory ascites.

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.