SBIR-STTR Award

We shall develop analytical tools for measuring the amount and speciation of zinc in semen; these tools will facilitate basic research and may lead to a zinc-based diagnostic kit for prostate cancer. According to the prevailing literature, semen zinc falls by 50 percent-90 percent in the early stages of prostate cancer while not changing in benign hypertrophy. If this is true, a combined measurement of semen zinc (falling in cancer) and serum PSA (rising in cancer) could provide sensitive and selective early diagnosis for prostate cancer. We envision test kits for routine testing of seminal zinc in the clinic, or even at home. Our Phase I goals are (i) develop methods and materials for measuring all the different seminal zinc pools (free, microligand-bound, protein bound, spermatozoan), (ii) establish preliminary norms for the various zinc pools in control men and (iii) measure the same parameters in samples from select prostate cancer patients. If Phase I results warrant continuation, in Phase II we will (i) prototype procedures for home/office kits for testing semen zinc, (ii) gather large-sample clinical data on zinc as a screening tool for prostate cancer (iii) develop quantitative models of the best multi-zinc pool diagnostic of cancer. PROPOSED COMMERCIAL APPLICATION: Commercial Potential: Yearly PSA testing is recommended for all men over 50, yet 40,000 men still die annually in the US alone from prostate cancer. If a zinc-based test were used along with PSA testing, the sales of the tests could be vast, and the contribution to men's health and wellness, equally vast.

Thesaurus Terms:
diagnosis design /evaluation, neoplasm /cancer diagnosis, prostate neoplasm, zinc clinical chemistry, method development, semen clinical research, human tissue, male

In Phase I we showed that our measurement of free zinc in expressed prostatic fluid is a promising clinical indicator of prostate cancer. Indeed, in our two pilot studies and one prior published study, prostatic fluid zinc scores gave areas under the receiver operating curve (AUROC) of .79, .92, and .99 for detecting biopsy-confirmed prostatic adenocarcinoma. Our test is non-invasive, requiring only a few drops of prostatic fluid obtained from the urethral meatus during a rectal prostate examination with brief prostate massage. The zinc measurement is fast, cheap, easy, and exquisitely accurate. Our Phase II study has two components. In Study IIA we will increase our sample size to better estimate the sensitivity and specificity of our test. We will collect samples of prostatic fluid from a carefully selected sample of approximately 100 men expected to have prostate adenocarcinoma and approximately 100 men expected to be cancer free. Upon histopathological confirmation of adenocarcinoma or the absence of adenocarcinoma in all men, a receiver operating curve analysis will be conducted to determine the sensitivity, specificity and overall area under the curve (AUROC) for the detection of adenocarcinoma by the measurement of zinc in prostatic fluid. This study will show how useful the zinc test is for detecting prostate cancer. The subjects in this study will be (i) men scheduled for prostatectomy (ii) men scheduled for cysto-prostatectomy (iii) men scheduled for saturation (64 core) needle biopsy and (iv) men scheduled for conventional biopsy. In Study IIB we will establish which prostatic disease conditions are accompanied by the loss of zinc sequestering and secretion. Thus, we will take tissue sections from the prostate glands of the subjects in Study IIA, stain them with H&E and (in some cases) antibodies to disease- defining proteins. Regions with specific prostatic pathology such as PIA (proliferative inflammatory atrophy), PIN (prostatic intraepithelial neoplasia) or adenocarcinoma will be marked on digital images of the sections, then adjacent sections will be imaged in X-RAY fluorescence and zinc histofluorescence microscopy to show the distribution of elemental and free zinc , respectively. Comparison of the classical histology with the zinc maps by digitally superimposing them will show how zinc sequestration (and therefore secretion) changes in each of the different types and stages of pathology. Data in the literature indicate that zinc sequestration and secretion are suppressed in PIN and suppressed in healthy-appearing acini that are near an adenocarcinoma, suggesting a field effect. If confirmed by our work, this would explain how even relatively small adenocarcinomas markedly suppress zinc secretion of the gland. Every year in the US about 1,500,000 prostate biopsies are done, revealing only about 300,000 cancers. Still, about 30,000 men die from cancers too advanced for effective treatment. We believe our zinc test could allow earlier and more certain detection of potentially aggressive cancers, thus saving lives. PUBLIC HEALTH NARAVTIVE: This Phase II SBIR is designed to determine the sensitivity and specificity of a zinc test for prostate cancer. The test measures zinc in massage-expressed prostatic fluid, and it only takes about 60 sec to get the fluid and about 60 sec to make the measurement on a table-top, $5000 instrument. The test is intended to supplement other tests, including the PSA and DRE. Because the zinc falls in cancer but does not fall in BPH, the zinc tests has the potential to distinguish these two conditions.

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