Modeling of the pH- and the temperature-dependant deviations of the free to total PSA (prostate specific antigen) ratios for clinical predictability of prostate cancer and benign prostate hyperplasia

Both the free and total PSA had been reported to be pH- and temperature-labile. We have introduced two submodels to describe the decay of PSAs. The overall pH-dependent decay model (OPDDM) describes the ratio of free to true scientific total PSA including both the immunoreactive and the nonimmunoreactive. We elucidated four pH-dependent formation constants for the free PSA with hydronium ion [H+], the PSA-ACT (α 1-antichymotrypsin), the PSA-API (α1-protease inhibitor), and the nonimmunoreactive PSA-AMG (α2- macroglobulin) complexes, respectively, to model the stability of the free to total PSA ratios. Model simulation indicated a highly pH-sensitive behavior of the free to total PSA ratios. While the temperature dependent decay model (TDDM) indicated that kinetically, free PSA revealed the most rapid decay rates due to its low activation energy, total PSA was shown to be relatively more thermally stable. The decay of all PSA species could be more accelerated at temperatures higher than -4°C, while it is kept below -70°C throughout. It is thus recommended to use the preparation fresh (better within 8 h) after venipuncture. And it is advisable that all the results are advised to perform corrections for each determination by calculating back to the data at the original physiological pH prior to clinical diagnostic interpretation.