PDIS – Photodynamic Infrared Spectroscopy
Fluorescence spectroscopic detection of single circulating cancer cells in the bloodstream
Objectives
Advances in cancer diagnostics play a pivotal role in increasing early detection of cancer and improving the chances of successful treatment. The clinical requirements for an objective, accurate and repeatable measurement of the pathological state of cancer patients after chemotherapy are overwhelming, because they directly influence the individual risks of metastasis formation and therefore the survival prognosis. The biophysical methods presently used in oncology for early cancer detection like MRT, US, CT, PET are able to detect tumors, which have a mass of at least 1 gram or more. However, a 1 g tumor consists of about 1 billion cells. Our new biophysical diagnostic method, which we call „Photodynamic Spectroscopy“ (PDS) combines the principles of Photodynamic Therapy and single-molecule spectroscopy at the ultimate quantum limit of one photon (1 cell).
The PDS blood screening can be performed with any other photosensitizers of significant quantum yield, like Chlorine e6, Curcumin, Hypericin, 5-ALA, Chlorophyllin. The applicability of all these photosensitizers depend mainly on the quantum yield, which can also be determined directly and easily by PDS.
Figure 4 depicts the measured photodynamic spectrum of Chlorine e6 in blood.
Figure 7: A patient during PDS- blood screening, the laser excitation was done via intravenous laser catheter, the spectroscopic detector was placed extravasal at the end of the optical laser fibre.
Discussion
When a solid tumor is formed and coupled to the blood vessel system (carcinoma in-situ), it starts to effuse tumor cells in the blood stream. Although lymph nodes acts as “filters”, it is proven that some cancer cells are able to pass through the lymph nodes. The lifetime of these cells in the blood is often very short, but it also can be very long (many years). It was found that patients with breast cancer have > 1000 cancer cells circulating in the bloodstream. (Silverstein M.J et al 1996) The basic idea of the PDS blood screening method is to control the blood with respect to the concentration of free circulating cancer cells. If the blood can be kept cancer cell-free, the probability of metastasis formation will be strongly reduced. Metastasis is the leading reason for the resultant mortality of patients with cancer. Cancer cells detected by the PDS screening can be easily removed by Chemotherapy or Photodynamic Therapy. This removal process again can be controlled by PDS. Consequently, the cancer patients can overcome the psychological uncertainty about their lifetime prognosis after primary surgery and chemotherapy.
The prerequisite for interpretation of the PDS blood screening spectra is the difference between the reference-spectrum and the verum-spectrum as result of the digital subtraction. A misinterpretation can only occur, when the reference-spectrum contains the emission of a cancer cell. In this case, no additional photon bursts would be detected, the result of the blood screening could be too positive and probably wrong. The probability that the reference-spectrum contains the photodynamic emission of a cancer cell depends on the concentration of cancer cells and can be estimated. When one single cancer cell is contained in the whole 5l blood, this cell will pass the laser spot during the verum screening period one times, because in 1000s the whole blood volume has passed the laser spot one times. The reference-spectrum is performed in 1 millisecond, the verum spectrum is measured in 1000s. Therefore, the probability that a cancer cell is passing the laser spot during the 1 ms reference-screening time is 1 ms /1000 s = 10 -6
The probability that a cancer cell emission is recorded during the reference-scan therefore is 1 to 1 million. Despite the very low probability, the PDS-verum scan is always repeated two times so that a total screening time is of 2000 s. That means that the probability of misinterpretation is further reduced to 1:2 Mill., a value which can be neglected for the clinical applications of the PDS-blood screening.
Conclusion
For the first time it becomes possible to evaluate by Photodynamic Spectroscopy (PDS), a biophysical method with ultimate resolution of one single cell, quantitatively and individually the efficacy of the surgical and chemotherapeutical cancer treatments
for cancer patients and (excluding leukemia) almost independent on the cancer type!
If there are remaining cancer cells/clusters in the blood, they can easily destroyed either by photodynamic therapy (PDT).In this procedure, the blood can be kept cancer cell-free, the probability of metastasis formation can be strongly reduced and the metastasis formation rate as the leading reason for the resultant mortality of cancer patients can be decreased.
All cancer patients get a significant reduction of their individual risk to develop cancer metastases at other organs and gain life quality due to the reduction of the psychological uncertainty of their lifetime prognosis!
We recommend to use PDS blood screening as diagnostic tool for the very early recognition of cancer formation and to integrate it in the annual check up procedure. In particular patients having a higher familiar or genetic cancerogenic risk should be controlled at least once a year.
