혈청 중의 TK(Thymidine Kinase) 활성을 방사성 동위원소(radioactive technique)를 사용하지 않고, 비색법에 의해 매우 고감도로 측정 할 수 있는 제품입니다. 혈청 중 TK 활성 상승은 종양질환 및 악성질환에 관련된 것으로 보고되고 있어, 세포분열 활동의 지표인 TK 활성을 측정함으로써 종양의 사전 예방 및 조기 치료와 치료의 효율성을 관찰하는 도구로써 사용될 수 있습니다.
TK is an enzyme converting deoxythymidine to deoxythymidine monophosphate. The main isoenzyme in the
circulation is expressed in the G1-S cell division stage to supply the thymidine triphosphate necessary for cell division.
Presence of active TK in serum and its correlation to tumour disease was shown 1982. Tests with lower sensitivity
from other manufacturers are used routinely in clinical laboratories. The following
reasons for elevated TK levels in
serum have been suggested: in addition to malignant disease also vitamin B12 deficiency, and certain virus infections.
With the high sensitivity obtained with DiviTum®, transient elevations during wound healing after e.g. surgery have
been reported. TK activity has also been found in body fluids other than serum, such as cerebrospinal fluid, pleural
fluid and ascitic fluid.
Assay Principle of DiviTum®
As substrate for TK the DiviTum® assay uses bromo-deoxyuridine which is phosphorylated to its monophosphate. To
immobilize and remove the monophosphate from the solution it is further phosphorylated to the tri-phosphate by
other kinases present in the reaction solution. The tri-phosphate is immobilized by DNA synthesis, in which a polyA
strand covalently bound to the microtiter plate well acts as template,
reverse transcriptase as the catalyst and odT as
the primer. After the TK activity incubation is completed, the plate is washed and incubated with an anti-
bromodeoxyuridine-antibody conjugated to alkaline phosphatase followed by a second wash. The amount of alkaline
phosphatase is evaluated using a chromogenic substrate, p-nitrophenyl phosphate (pNPP). The assay measures the
activity of the enzyme. The TK activity is given as Du/L. 1000 Du/L corresponds to the activity in a solution
containing 1000 ng/L of a
reference sample of recombinant TK.
DiviTum™ – Important Features
• Measures the growth rate of a tumor with unique sensitivity and precision – using a simple blood sample
• A predictive marker for therapy response, disease progression and overall survival in solid tumors
• Demonstrates precise prognostic capabilities in several forms of solid tumors
• Can be an attractive companion diagnostic for pharma companies in research projects when evaluating
Important areas of use
One of the most important applications for the TK test has historically been in non-Hodgkin’s lymphoma and in
chronic lymphocytic leukaemia. TK levels can give an early warning of recurrence of the disease, allowing timely
In myelodysplastic syndrome, the TK value is fundamental for the choice of treatment, as it gives a reliable indication
of the risk for transformation to acute myeloid leukaemia.
In patients with breast cancer, the DiviTum™ value can predict response to therapy and outcome at certain cut-off
levels, as demonstrated in a recent trial by Karolinska Institutet. This information can affect the choice of treatment
and facilitate tailored therapy for the patient.
The assay defines the TK activity on the basis of the amount of DNA produced and quantified using an ELISA
technique. The TK activity is not strictly proportional to the TK concentration present and thus the assay should
always be performed using the amount of serum and incubation times given in this Instruction for Use. The DiviTum®
assay has an analytical sensitivity of 10 Du/L (LLD) / 50 Du/L (LLQ). The working
range extends up to 5000 Du/L.
The precision (CV) at 100Du/L is better than 20%.
Fig 1. Typical standard curve after 3 hours incubation time
Figure 2. shows the distribution of serum TK activity of 240 apparently healthy blood donors in 12 age groups
(10 men and 10 women in each group), measured with the DiviTum® kit.
Figure 3. Correlation between values obtained with DiviTum® and Prolifigen® for tumour bank samples analysed.
The data in figure 2 show that the 90th percentile corresponds to approximately 80 Du/L and the 80th percentile to
approximately 50 Du/L. This was a closed study and a second sample to exclude transient TK increase could not be
obtained. Half of the blood donors were over 50 years old. Therefore, it is probable that a certain proportion of them
have tumour disease not yet diagnosed but still influencing their TK
values and also that there are some cases of viral
infections among the blood donors. This makes it reasonable to use the 80th percentile, corresponding to 50 Du/L,
as the upper limit of the reference range.
- Adhesive tape cover
- Microtiter plate lid
- Pipetting tray
- Sample dilution plate with 96 wells
- Immunosorbent microtiter plate with 96 wells
- Sample diluent - ready to use
- Reagent A / B
- Control low / high
- Solution - ready to use
- Washing buffer - 80 x concentrate
- Enzyme conjugate diluent
- Enzyme conjugate
- Substrate buffer
- Enzyme conjugate substrate
* Each kit contains materials for analysis of 38 samples including controls in duplicate (2×10 µL is required of
Instruction sheet (PDF)
Clinical Study (Published studies)
Background and use in gene therapy (PDF)
The quantitative assay for TK and its clinical use (PDF)
Use of TK assay in serum, plasma and other body fluids (PDF)