New prospective for non-invasive detection, grading, size evaluation, and tumor location of prostate cancer.

BACKGROUND: PSA blood test and other present screening tools fail to provide the required sensitivity and specificity and, at early stages, lack correlation with tumor grade, volume, and location. Thus alternative approaches are highly desired. We present and assess a novel method for PCa detection, grading, volume evaluation and tumor location, based on non-invasive zinc concentration mapping in the gland by means of a dedicated rectal probe. METHODS: Zinc-concentration values measured in histologically examined tissue fragments from needle biopsy of 598 patients were analyzed. They were used to generate computer simulated zinc-concentration maps, further analyzed with image-processing tools. The tumor detection performances versus Gleason grade were assessed. RESULTS: A significant increase of zinc depletion with increasing Gleason pattern (grade) classification was established. Tumor detection performance in zinc-concentration maps progressively improves with the cancer's first component score. Reliable information on the location, size and Gleason-grade combination of the lesion can be extracted for clinically relevant volumes. CONCLUSIONS: Zinc depletion in the prostate peripheral zone is the basis for a novel, non-invasive PCa detection, localization, volume evaluation and grading method. Its realization and application as a pre-biopsy and pre-treatment examination, or a follow-up tool, relies on the development of a dedicated transrectal probe. It should have significant impact on biopsy effectiveness, point at a possible extraprostatic extension and provide critical data for focal treatment. The information on tumor grade and distribution may have an important impact on disease management.

X-ray fluorescence-based differentiation of neck tissues in a bovine model: implications for potential intraoperative use.

This study explores the possibility of using X-ray fluorescence (XRF)-based trace-element analysis for differentiation of various bovine neck tissues. It is motivated by the requirement for an intra-operative in-vivo method for identifying parathyroid glands, particularly beneficial in surgery in the central neck-compartment. Using a dedicated X-ray spectral analysis, we examined ex-vivo XRF spectra from various histologically verified fresh neck tissues from cow, which was chosen as the animal model; these tissues included fat, muscle, thyroid, parathyroid, lymph nodes, thymus and salivary gland. The data for six trace elements K, Fe, Zn, Br, Rb and I, provided the basis for tissue identification by using multi-parameter analysis of the recorded XRF spectra. It is shown that the combination of XRF signals from these elements is sufficient for a reliable tissue differentiation. The average total abundance of these trace elements was evaluated in each tissue type, including parathyroid and salivary gland for the first time. It is shown that some tissues can unequivocally be identified on the basis of the abundance of a single element, for example, iodine and zinc for the identification of thyroid gland and muscle, respectively.

In vivo determination of prostatic zinc: phantom feasibility study.

This paper describes a phantom-based feasibility study for a potential in vivo determination of zinc in prostate, which could bring about improved diagnosis of prostate cancer. An x-ray fluorescence topographic technique was developed, which will permit determination of the Zn content in the prostate through the rectum, namely behind a 2-3 mm thick layer of the rectal wall. The topographic approach, together with a reconstruction method developed here, minimizes the interference of Zn from non-prostatic tissue. The phantom studies show that it will be possible to determine Zn in a prostatic compartment behind a few mm thick layer of tissue using a specially designed transrectal probe. Such a probe is currently under development in our laboratories.

Clinical assessment of the cancer diagnostic value of prostatic zinc: a comprehensive needle-biopsy study.

BACKGROUND: The correlation between Zinc concentration in the prostate's peripheral zone to the onset or presence of malignant process needs to be evaluated in detail. METHODS: Zinc concentration was measured in approximately 1-4 mm3 segments of fresh needle-biopsy cores, with X-ray fluorescence, and correlated with the histological findings of these tissue segments. RESULTS: Local Zinc concentration is correlated with the presence of cancer (PCa); the higher the Gleason score the greater the Local Zinc depletion. The Zinc value averaged over the entire extracted tissue is specific only to Gleason score 8-9 PCa. The results refer to patients avoiding Zinc-rich supplements since those show elevated prostatic Zinc concentration in identified cancer tissue. A computer simulation analysis of randomly located 0.03-3.3 cm3 lesions, with particular Gleason score and the measured Local Zinc concentration, revealed a potential diagnostic approach definitely superior to PSA, with sensitivity to the tumor grade and with excellent detection capability for Gleason score >6. Further clinical studies have been designed, both on full prostates after radical prostatectomy as well as on biopsy cores at higher resolution, to establish the accuracy of the method for Gleason score = 6. CONCLUSIONS: The PCa diagnostic potential of Local Zinc concentration is confirmed and there is indication that the amount of Zinc depletion could be used as a measure of the Gleason score of the tumor. Local Zinc concentration mapping has the potential to improve patient selection for biopsy, biopsy site selection and local therapy (e.g., Cryotherapy, Brachytherapy) site selection.

XRF study of archaeological and metallurgical material from an ancient copper-smelting site near Ein-Yahav, Israel.

A movable XRF instrument (a bench-top designed machine modified to work in the field for archaeological purposes) was used for analysis of artifacts and sediments during the field study (01-07 April 2003) of a small copper-smelting site in the Negev (about 30km west of the Feinan complex of ancient copper mines and smelting sites in Jordan). The site consists of a relatively small hill with blackened slopes, covered mainly by crushed copper slag. The surface collection of datable objects (i.e. pottery shards and stone tools) indicated that the site had functioned at the end of the Early Bronze Age and during the Roman/Byzantine time. The analysis of Cu concentration in the ash and in the ground as well as the analysis of ore and slag, were used as markers for the identification of the operation centers and for locating the remains of the smelting devices used at the end of the Early Bronze Age for smelting copper. The ore in use typically contained 35-45% Cu, up to 1% Mn and up to several percent Fe. The slag contained 13-20% Mn and 1-5% Cu and Fe. From these results we are able to estimate the Cu production scale during the first and most active period on this site, at the end of the Early Bronze Age.

Prostatic Zn determination for prostate cancer diagnosis.

We present our studies of prostatic Zn concentration measurements, carried out in the light of a novel prostate cancer (CAP) diagnosis method proposed by us. The method is based on in vivo prostatic Zn mapping by XRF trans-rectal probe. We report on the extensive clinical studies, intended to assess the validity of the novel proposed diagnostic method. Zn content was measured in vitro in needle-biopsy samples from several hundreds of patients, and was correlated with histological findings and other patient parameters. For this purpose, a technique of absolute Zn content determination in approximately 1mm(3) fresh tissue samples by XRF was developed. The experimental details and the main clinical-evaluation results are presented. We further outline the suggested design of the XRF trans-rectal probe for an efficient in vivo detection and mapping of the Zn fluorescence radiation from the prostate through the rectal wall. Laboratory phantom studies, a preliminary design concept and its expected performance are also reported.

Prostatic zinc and prostate specific antigen: an experimental evaluation of their combined diagnostic value.

PURPOSE: In cancer affected prostate cells lose the ability to concentrate zinc, resulting in a substantial decrease in Zn in the prostate. We investigated the possibility of using prostatic zinc combined with prostate specific antigen (PSA) as a novel tool for the reliable diagnosis of prostate cancer. MATERIALS AND METHODS: Using the x-ray fluorescence method the Zn concentration was determined in vitro in prostate samples extracted by surgery from 28 patients. Clinical records included age, serum PSA, sextant prostate needle biopsy, previous medical therapy, surgical procedure and histological findings. RESULTS: A new relationship was found between Zn in prostate tissue and PSA in blood, which allows improved separation between prostate cancer and benign prostate hyperplasia, and might have a significant impact on the reliable diagnosis of prostate cancer. CONCLUSIONS: Zn concentration is not uniform even in the same anatomical region of the prostate, so that a number of measurements at various locations are required for a diagnostic procedure. The most interesting finding in this study is the relationship between Zn concentration and PSA. A combination of these parameters represents a significant improvement on the diagnostic value of each of them separately and provides a powerful tool for more accurate diagnosis. Although the method may be applied in vitro on biopsy samples, our study underlines the importance of developing a facility for in vivo Zn determination in the prostate.