Charles F. Gottlieb

Interstitial microwave hyperthermia applicators having submillimetre diameters

Using microscopic techniques we have fabricated interstitial hyperthermia applicators having diameters of 0.20, 0.33 and 0.58 mm, which will fit through catheters of 30, 26 and 22 gauge, respectively. Existing commercial applicators having a diameter of 1.1 mm required 17 gauge (or larger) catheters. Our new applicators, which operate at 915 MHz, are a smaller version of a design used by others. We have characterized our applicators by determining the energy deposition patterns (SAR) in muscle-simulating phantoms. These patterns were determined by measuring the electric field intensity using a miniature implantable isotropic probe having a diameter of 3 mm. Contours of the SAR data for our applicators, as well as a larger commercial applicator, show that all of these applicators exhibit similar heating patterns. Test results suggest that the durability and power handling capability of our submillimetre applicators are adequate for use in patients. Our new applicators should be useful in the percutaneous treatment of deep-seated tumours, intraoperative treatments, and also permit intraluminal or intravascular access to tumours.

Investigation of different combinations of estrogen therapy and radiation therapy on prostatic adenocarcinoma (R-3327).

The relative effectiveness of different combinations of estrogen therapy and radiation therapy against the R-3327 prostatic adenocarcinoma of the Copenhagen rat was studied. Because of similar actions of estrogens and radiation in the cell cycle, and possibly antagonistic effects reported in the clinical literature, we looked for an antagonism between these two therapeutic modalities. Radiation therapy consistently showed a greater tumor inhibitory effect than estrogen therapy alone at the dose tested. Combinations of radiation therapy with hormonal manipulation did not appear to show a greater inhibition of tumor growth than radiation therapy alone. There also did not appear to be an antagonistic effect between these two modalities in this system.

The use of ATP bioluminescence assay and flow cytometry in predicting radiosensitivity of uterine cancer cell lines: Correlation of radiotoxicity and cell cycle kinetics

Abstract Radiotherapy remains an important part of uterine cancer treatment. This study was designed to evaluate the potential of the ATP bioluminescence assay and flow cytometry for predicting radiosensitivity. Correlation of these two modalities revealed important insights into the relationship of radiotoxicity and cell kinetic effects. Six human uterine cancer cell lines were used: AE7, ECC1, HEC1A, HEC1B, AN3, and SKUT1B. Doses of cobalt 60 were 0, 1, 2, 5, 8, and 10 Gy. The ATP bioluminescence assays were performed on Day 7. Cell samples were taken at 0, 24, 48, 72, 96, and 168 hr for flow cytometry. The linear-quadratic model was used to fit survival data and mean inactivation dose D was calculated. Among parameters such as D, α and β coefficients, and surviving fraction at 2 Gy (SF2), both D and SF2 correlated best with survival data. Radiation effects on the cell cycle did not correlate with D and revealed two distinct patterns: either a G1 accumulation with mild G2 block or a G1 depletion and severe G2 block. The S cells consistently demonstrated a biphasic pattern with an initial reduction followed by an accumulation. In summary, the ATP assay was shown to have potential in the study of radiosensitivity. Radiation-induced cell kinetics appeared to vary with intrinsic cellular differences and, thus, could not be used to predict radiosensitivity.

Cell kinetic perturbations after irradiation and caffeine in the BG-1 ovarian carcinoma cell line

The treatment of ovarian carcinoma includes maximum surgical removal of the tumor tissue followed by irradiation or chemotherapy. In this study, the effects of caffeine on cell cycle traverse have been studied over a 168-hr period after X irradiation in BG-1 cells, an ovarian carcinoma cell line. The results were obtained with dual-parameter flow cytometric measurements of DNA and nuclear protein, using propidium iodide and fluorescein isothiocyanate. After radiation alone, a dose-related arrest of cells in G2 phase and cell kill were observed. Irradiating BG-1 cells with 5 Gy produced an accumulation of the cells in G2 at 24-72 hr postirradiation. When G2 was divided into low nuclear protein (G2A) and high nuclear protein (G2B) compartments, there was a G2A peak accumulation at 24 hr and a G2B peak accumulation at 48-72 hr. The addition of 1 mM caffeine to the culture media, starting immediately postirradiation, prevented G2 arrest, promoting a rapid traverse of cells through G2A to G2B to G1, which was associated with diminished survival.

Evaluation of heating patterns of microwave interstitial applicators using miniature electric field and fluoroptic temperature probes

The SAR patterns were determined for four commercially available microwave (915 MHz) interstitial applicators. Values of SAR were determined using a miniature (3 mm diameter) implantable isotropic electric field probe or a custom 0.25 mm diameter fluoroptic temperature probe. These are the smallest such probes that are currently available. Similar radial variation of SAR was found at the axial position of the gap in the outer conductor for each applicator. Electric field probe measurements are much faster and avoid some of the errors caused by the rapid spatial variation of SAR with interstitial applicators. The major limitation on the electric field probe is its size; it is larger than the applicators being tested.

Computer Controlled Hyperthermia Unit for Cancer Therapy

A versatile hyperthermia control system, based on a microcomputer, provides automated temperature regulation (1 channel) and monitoring (3 channels) and control of microwave output (both on/off and power level), and displays temperature (degree C) and microwave output (watts) graphically in real time; all data are stored on floppy diskette.

Preclinical Evaluation of Submillimeter Diameter Microwave Interstitial Hyperthermia Applicators

Ultra miniature coaxial cable has been used, with microscopic techniques, to fabricate interstitial hyperthermia applicators having diameters of 0.20 mm, 0.33 mm, and 0.58 mm; commercial applicators have a diameter of 1.1 mm. Animal studies with the 0.33 mm diameter applicators have shown that they produce less local tissue trauma than the larger-diameter devices. All of these applicators operate at 915 MHz and have similar heating patterns because they use the conventional monopole design and the catheters have been approximately scaled to the dimensions of each size applicator. We have measured the heating (SAR) patterns of these applicators in tissue-simulating phantoms, both singly and in arrays, using a miniature electric field probe. As an intermediate step to patient trials, we have examined the ability of these applicators to provide effective heating of perfused tissue, using pig thigh and liver as models. Test results suggest that the durability and power handling capabilities of our submillimeter applicators are adequate for use in patients. These new applicators should be useful in the percutaneous treatment of deep-seated tumors and in intraoperative treatments. The applicators also permit intraluminal or intravascular access to tumors.