A new alpha-particle irradiator with absolute dosimetric determination.

A new experimental setup for uniform alpha-particle irradiation of cells in vitro is described. The alpha-particle irradiator is based on a radioactive (212)Pb/(212)Bi source. In the experimental setup proposed, cells are grown directly on a polylysine-coated track-etch material that forms the base of custom-made cell dishes. Alpha-particle irradiation is done through the base of the dish. Immediately prior to irradiation, the cell dish is scanned under a microscope, and images of cells with the corresponding coordinates are saved. After irradiation and after the biological end point under study has been determined, the cell dish is etched to develop alpha-particle tracks in the dish base. A microscope image series of alpha-particle track images is obtained by accurately revisiting every original (preirradiation) cell position in the track-etched dish. The number of alpha-particle traversals of each individual cell is scored by mapping images of alpha-particle tracks onto the images of cells recorded prior to irradiation. The uncertainty of the alpha-particle hit determination is 0.9 microm. The procedure described thus presents a method for radiobiological experiments with absolute, rather than statistical, cell dosimetry.

212Bi-DOTMP: an alpha particle emitting bone-seeking agent for targeted radiotherapy.

The synthesis and in vivo stability of the bone-seeking alpha-particle emitting compounds 212Bi-DOTMP and 212Pb/212Bi-DOTMP are described. 212Bi-DOTMP, injected i.v. into Balb/c mice, showed prominent bone localization and a rapid clearance from blood and other organs. Femur/blood ratios increased from 13 at 15 min up to 490 at 2.0 h postinjection. Enhanced uptake of 212Bi-DOTMP was demonstrated in regions with high bone turnover. A comparison between 212Bi-DOTMP and [153Sm]Sm-EDTMP showed essentially no differences in biodistribution. 212Pb/212Bi-DOTMP followed a similar biodistribution, except for slightly elevated levels of 212Bi in the kidneys. The present study has shown 212Bi-DOTMP to be an in vivo stable bone-seeking radiopharmaceutical with promising biological properties for the treatment of sclerotic metastases and osteoblastic osteosarcoma.

Synthesis, purification and biodistribution of (205)Bi-DOTMP, visualizing bone deposition patterns with autoradiography.

A HPLC system has been developed for carrier free and rapid delivery in a physiological buffer of the alpha-particle emitting bone-seeking radiopharmaceutical (212)Bi-DOTMP. (205)Bi-DOTMP was synthesized and HPLC purified to mimic and visualize the deposition pattern in bony tissues of (212)Bi-DOTMP by autoradiography. Inhomogeneous bone deposits were found with the highest concentration in the bone matrix, the endosteum and in the growth zones of young mice. Analysis of urine samples showed that (205)Bi-DOTMP was cleared as an intact complex.

Survival of human lung epithelial cells following in vitro alpha-particle irradiation with absolute determination of the number of alpha-particle traversals of individual cells.

PURPOSE: To throw light on human exposure to domestic radon and radon progeny, the effects of low doses of alpha-particle irradiation on normal human lung epithelial cells has been studied. At such low exposure levels the concept of dose is inadequate due to the stochastic variation in the number of alpha-particle traversals per cell. The objective of the current study was to establish an accurate survival curve for human lung epithelial cells with absolute determination of the exact number of alpha-particle traversals of individual cells. MATERIALS AND METHODS: Irradiation of L132 cells growing in tracketch detector-based cell dishes, was performed using a collimated alpha-particle beam from a 210Po source. The number of alpha-particle traversals through each individual cell was scored by using a technique of retrospective track-etch dosimetry. This technique is based upon image matching and mapping of corresponding cell and alpha-particle track images. The spatial resolution of the hit determination procedure was +/-0.9/microm. RESULTS: Surviving fractions of cells (SF) showed strict dependence on the number of nuclear traversals (n), with SF(n)= a exp(-bn), a=0.957 (+/- 0.046), b = 0.587 (+/- 0.059), R2 =98.8%. No significant dependence on the number of nuclear membrane traversals (m) or the number of cytoplasm traversals (c) was observed.

Predicting detectability in radioguided surgery: a study based on physical characterization of the probe and on tissue uptake ratios of 125I-, 153Sm- and 165Er-labelled radiopharmaceuticals.

We performed measurements of the sensitivity in water of the radioguided surgery system, Neoprobe 1000. Point sources of 125I, 153Sm and 165Er were measured to a geometric accuracy of 0.1 mm. These measurements were performed with the detector uncollimated and with two different collimators; the results were used to construct three-dimensional sensitivity matrices from which isosensitivity curves could be derived. The matrices were used to simulate the reliability of detecting tumours of various sizes, at various depths, and with variable uptake ratios and activity levels of the three radionuclides investigated. Simulations showed improved tumour detection with a conical collimator, demonstrating that collimator design is important. To minimize the radiation dose during diagnostic work-up, a novel bone-seeking radiopharmaceutical, 165Er-EDTMP, was developed and tested. It showed rapid bone localization, especially in growth zones, and rapid clearance from blood and non-osseous tissues. Its biodistribution was similar to that of 153Sm-EDTMP. Based on these results and previous clinical data, the simulations predicted that lung metastases with a radius of 1 mm might be reliably detected with the Neoprobe 1000 system, if equipped with a suitable collimator.

A 212Pb generator based on a 228Th source.

A two-compartment 212Pb generator has been constructed and characterized physically and chemically. It is based on transport by airflow of gaseous 220Rn emanating from thin layers of [228Th]barium stearate. 220Rn is collected in a glass bubbler by extraction into an organic solvent and solidified at temperatures below -72 degrees C. Tracer studies show that the decay product 212Pb can be recovered with approximately 70% yield. It is suggested that this generator design could accommodate therapeutic levels of 212Pb/228Th.

A novel 210Po-based alpha-particle irradiator for radiobiological experiments with retrospective alpha-particle hit per cell determination.

A new experimental design for alpha-particle irradiation of cells in vitro is described where the alpha-particle irradiator is based on a 210Po radioactive source. In the described set-up cells are grown directly on an alpha-particle detector and irradiation is done from below. For an irradiated cell dish the number of alpha-particle traversals through each individual cell is scored by using retrospective track etch dosimetry and an accurate technique for individual cell relocation. Calibration experiments characterizing the new irradiator system are presented.