JP7589935B2 - Analysis device and analysis program - Google Patents

Description

Embodiments of the present invention relate to an analysis device and an analysis program.

Conventionally, tests are conducted to detect specific substances in the body, such as genes and proteins, in order to select the appropriate anticancer drug for a patient. In particular, when it comes to predicting the efficacy of the metabolic antagonist 5-FU (Fluorouracil), it has been reported that there is a relationship between the expression level of TS (Thymidylate synthase), an inhibitory target of 5-FU, and the sensitivity of 5-FU. Therefore, it is believed that the efficacy of 5-FU can be predicted to some extent by evaluating the expression level of TS in the patient's pathological tissue.

However, when evaluating the expression level of TS, pathological tissue from the patient is generally obtained by tissue biopsy and then stained with a prescribed staining method, so the evaluation of the expression level of TS places a heavy burden on the patient due to its high invasiveness. Moreover, because tissue biopsy only targets a portion of the tumor, it is difficult to evaluate the comprehensive pharmacokinetics and efficacy of 5-FU in tumors with heterogeneity when evaluating the expression level of TS.

JP 2015-044803 A

Johnston PG, Lenz HJ, Leichman CG, Danenberg KD, Allegra CJ, Danenberg PV, Leichman L., Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors., Cancer Res. 1995 Apr 1;55(7):1407-12. Tsutani Y, Yoshida K, Sanada Y, Wada Y, Konishi K, Fukushima M, Okada M., Decrease orotate phosphoribosyltransferase activity produces 5-fluorouracil resistance in a human gastric cancer cell line., Oncol Rep. 2008 Dec;20(6) :1545-51.

The problem that this invention aims to solve is to make it possible to evaluate the comprehensive pharmacokinetics and efficacy of 5-FU without imposing a burden on the patient.

The analysis device according to the embodiment includes an extraction unit, a calculation unit, and an evaluation unit. The extraction unit extracts detection values in the tumor region, blood region, and muscle region from a nuclear medicine image of a subject administered a radioactively labeled anticancer drug that is effective by accumulating in tumors. The calculation unit calculates a first comparison value that is a comparison result between the detection value in the blood region and the detection value in the tumor region, and a second comparison value that is a comparison result between the detection value in the muscle region and the detection value in the tumor region. The evaluation unit evaluates the accumulation of the drug in the tumor based on the first comparison value and the second comparison value calculated by the calculation unit.

FIG. 1 is a block diagram showing an example of the configuration of a medical image diagnostic system according to an embodiment. FIG. 2 is a flowchart illustrating an example of a flow of a process executed by the analysis device according to the embodiment. FIG. 3 shows the structural formula of [18F]5-FU. FIG. 4 shows examples of PET images of DLD-1 mice and DLD-1/5-FU mice administered with [18F]5-FU. FIG. 5 is a diagram showing an example of an image obtained by superimposing a CT image and a PET image. FIG. 6 is a graph showing the time course of the accumulation of [18F] in tumors of DLD-1 mice and DLD-1/5-FU mice administered with [18F]5-FU. FIG. 7 is a graph showing the tumor-blood ratios in DLD-1 mice and DLD-1/5-FU mice, calculated from the distribution of radioactivity in the tumor and blood. FIG. 8 is a graph showing the tumor-muscle ratios in DLD-1 mice and DLD-1/5-FU mice, calculated from the distribution of radioactivity in the tumor and muscle.

Below, embodiments of the analysis device and analysis program will be described in detail with reference to the drawings. Note that the embodiments are not limited to the following embodiments.

(Embodiment)
The analysis device according to the embodiment includes an extraction unit, a calculation unit, and an evaluation unit. The extraction unit extracts detection values in a tumor region, a blood region, and a muscle region from a nuclear medicine image of a subject administered with a radioactively labeled anticancer drug that is effective by accumulating in a tumor. The calculation unit calculates a first comparison value that is a comparison result between the detection value in the blood region and the detection value in the tumor region, and a second comparison value that is a comparison result between the detection value in the muscle region and the detection value in the tumor region. The evaluation unit evaluates the accumulation of the drug in the tumor based on the first comparison value and the second comparison value calculated by the calculation unit. The first comparison value may be a ratio between the detection value in the blood region and the detection value in the tumor region. The second comparison value may be a ratio between the detection value in the muscle region and the detection value in the tumor region.

Fig. 1 is a block diagram showing an example of the configuration of a medical image diagnostic system according to an embodiment. As shown in Fig. 1, a medical image diagnostic system 10 according to an embodiment includes a medical image diagnostic device 100 and an analysis device 200. The medical image diagnostic device 100 and the analysis device 200 are communicatively connected via a network 300 such as an in-hospital LAN (Local Area Network).

In the following embodiment, a case will be described in which a PET-CT device that integrates a PET (Positron Emission computed Tomography) device and an X-ray CT (Computed Tomography) device is applied as the medical image diagnostic device 100, but the embodiment is not limited to this, and for example, a PET device may be applied as the medical image diagnostic device 100. Furthermore, when a PET device is applied as the medical image diagnostic device 100, the medical image diagnostic system 10 may further include an X-ray CT device as a medical image diagnostic device separate from the medical image diagnostic device 100.

The medical image diagnostic device 100 is a device that captures medical images. The medical image diagnostic device 100 captures medical images depicting the inside of the body of a subject, and transmits the captured medical images to the analysis device 200. For example, the medical image diagnostic device 100 captures PET images depicting the inside of a subject having a tumor to which an anticancer drug 5-FU ([18F]5-FU) labeled with a positron-emitting nuclide 18F has been administered, and transmits the captured PET images to the analysis device 200. More specifically, the medical image diagnostic device 100 captures PET images of a subject having a tumor after a certain time has elapsed since administration of [18F]5-FU, and transmits the captured PET images to the analysis device 200. The medical image diagnostic device 100 also captures CT images depicting the inside of a subject having a tumor, and transmits the captured CT images to the analysis device 200. A 5-FU degrading enzyme inhibitor may be administered to the subject together with [18F]5-FU. [18F]5-FU is an example of a drug in which 5-FU, an anticancer drug that is effective by accumulating in tumors, is radioactively labeled. The subject may be one in which it is unclear whether or not it has a tumor. The PET image is an example of a nuclear medicine image.

The analysis device 200 acquires medical images via the network 300, and executes various processes using the acquired medical images. For example, the analysis device 200 acquires PET images and CT images of a subject having a tumor to which [18F]5-FU has been administered via the network 300, and executes various processes using the acquired PET images and CT images. The analysis device 200 executes a processing function for making it possible to evaluate the comprehensive pharmacokinetics of 5-FU and the efficacy of 5-FU without imposing a burden on the patient. The analysis device 200 is realized, for example, by a computer device such as a workstation.

As shown in FIG. 1, the analysis device 200 has a network interface 201, an input interface 202, a display 203, a memory circuit 204, and a processing circuit 205. The network interface 201, the input interface 202, the display 203, the memory circuit 204, and the processing circuit 205 are connected to each other.

The network interface 201 receives medical images. The medical images received by the network interface 201 are stored in the memory circuitry 204.

The input interface 202 accepts various input operations from an operator, converts the accepted input operations into electrical signals, and outputs the electrical signals to the processing circuit 205. For example, the input interface 202 is realized by a mouse, keyboard, trackball, switch, button, joystick, a touchpad that performs input operations by touching the operation surface, a touchscreen that integrates a display screen and a touchpad, a non-contact input circuit that uses an optical sensor, a voice input circuit, and the like. Note that the input interface 202 is not limited to those that have physical operating parts such as a mouse and keyboard. For example, an electrical signal processing circuit that receives an electrical signal corresponding to an input operation from an external input device provided separately from the analysis device 200 and outputs the electrical signal to the processing circuit 205 is also included as an example of the input interface 202.

The display 203 displays various information. For example, the display 203 displays medical images, etc. under the control of the processing circuit 205. The display 203 displays a GUI (Graphical User Interface) for receiving various instructions and settings, etc. from the operator via the input interface 202. For example, the display 203 is a liquid crystal display or a CRT (Cathode Ray Tube) display. The display 203 may be a desktop type, or may be configured as a tablet terminal or the like capable of wireless communication with the main body of the analysis device 200. The display 203 is an example of a display unit.

The memory circuitry 204 is realized, for example, by a semiconductor memory element such as a random access memory (RAM), a flash memory, a hard disk, an optical disk, or the like. The memory circuitry 204 is also used as a non-transient storage medium by hardware. The memory circuitry 204 stores acquired medical image data. Also, for example, the memory circuitry 204 stores a program for enabling the circuits included in the analysis device 200 to realize their functions. The memory circuitry 204 is an example of a memory unit.

The processing circuitry 205 controls the overall processing of the analysis device 200. More specifically, the processing circuitry 205 has a display control function 205a, a reception function 205b, an extraction function 205c, a calculation function 205d, and an evaluation function 205e. The display control function 205a is an example of a display control unit. The reception function 205b is an example of a reception unit. The extraction function 205c is an example of an extraction unit. The calculation function 205d is an example of a calculation unit. The evaluation function 205e is an example of an evaluation unit.

Here, for example, each processing function of the processing circuit 205, the display control function 205a, the reception function 205b, the extraction function 205c, the calculation function 205d, and the evaluation function 205e, are stored in the storage circuit 204 in the form of a program executable by a computer. The processing circuit 205 reads each program from the storage circuit 204 and executes each read program to realize the function corresponding to each program. In other words, the processing circuit 205 in the state in which each program is read has each function shown in the processing circuit 205 in FIG. 1. Note that in FIG. 1, it has been described that each processing function of the display control function 205a, the reception function 205b, the extraction function 205c, the calculation function 205d, and the evaluation function 205e is realized by a single processing circuit 205, but the processing circuit 205 may be configured by combining multiple independent processors, and each processor may execute each program to realize each processing function.

The term "processor" used in the above description refers to circuits such as a CPU (Central Processing Unit), a GPU (Graphics Processing Unit), an Application Specific Integrated Circuit (ASIC), a programmable logic device (e.g., a Simple Programmable Logic Device (SPLD), a Complex Programmable Logic Device (CPLD), and a Field Programmable Gate Array (FPGA)). Note that instead of storing a program in the memory circuit 204, the processor may be configured to directly incorporate the program into its circuitry. In this case, the processor realizes its function by reading and executing the program incorporated into the circuitry.

The display control function 205a causes various GUIs or medical images, etc., to be displayed on the display 203. For example, the display control function 205a causes various GUIs, PET images, CT images, or superimposed images of PET images and CT images, etc., to be displayed on the display 203.

The reception function 205b receives various operations by the operator via the input interface 202. For example, the reception function 205b receives an operation by the operator to set a region of interest within a tissue region via the input interface 202. More specifically, the reception function 205b receives an operation by the operator to set a region of interest within a tumor region, a heart region, and a muscle region via the input interface 202. The reception function 205b sends the received region of interest to the extraction function 205c. The heart region is an example of a blood region.

The extraction function 205c extracts radioactivity values within regions of interest set within the tissue region from a PET image of a subject having a tumor to which [18F]5-FU has been administered. For example, the extraction function 205c extracts radioactivity values (e.g., average radioactivity values, etc.) within a region of interest set within the tumor region (tumor region of interest), a region of interest set within the heart region (heart region of interest), and a region of interest set within the muscle region (muscle region of interest) from a PET image of a subject having a tumor to which [18F]5-FU has been administered. Note that the radioactivity values are an example of detection values.

The calculation function 205d calculates a first ratio, which is the ratio of the radioactivity value in the tumor region of interest to the radioactivity value in the heart region of interest, and a second ratio, which is the ratio of the radioactivity value in the tumor region of interest to the radioactivity value in the muscle region of interest, from the radioactivity values in the tumor region of interest, heart region of interest, and muscle region of interest extracted by the extraction function 205c. Note that the first ratio is an example of the ratio of the detection value in the blood region to the detection value in the tumor region. Also, the second ratio is an example of the ratio of the detection value in the muscle region to the detection value in the tumor region.

The evaluation function 205e evaluates the specificity of the accumulation of [18F]5-FU in the tumor from the first ratio and the second ratio calculated by the calculation function 205d. For example, the evaluation function 205e evaluates whether there is a tendency for [18F]5-FU to accumulate in the tumor by comparing the first ratio and the second ratio calculated by the calculation function 205d with a predetermined threshold (e.g., 1, etc.). The threshold may be set, for example, based on the first ratio and the second ratio obtained from a certain number of patients. Also, evaluating the specificity from the first ratio and the second ratio is an example of evaluating the accumulation of the drug in the tumor based on the ratio of the detection value in the blood region to the detection value in the tumor region and the ratio of the detection value in the muscle region to the detection value in the tumor region.

Next, an example of the flow of processing executed by the analysis device 200 according to the embodiment will be described. FIG. 2 is a flowchart showing an example of the flow of processing executed by the analysis device 200 according to the embodiment. Note that this description is based on the premise that PET images and CT images obtained by administering [18F]5-FU to a subject having a tumor and imaging the subject using the medical image diagnostic device 100 a certain time after administration have been stored in advance in the memory circuitry 204.

First, the display control function 205a causes the display 203 to display the CT image stored in the memory circuitry 204 (S1). The display control function 205a may also cause the display 203 to display a superimposed image of the PET image and the CT image.

The operator confirms the positions of the subject's tumor, heart as a blood pool, and muscles from the CT image displayed on the display 203. The operator performs an operation to set a region of interest within the tumor region, heart region, and muscle region in the image via the input interface 202. Note that if a superimposed image is displayed on the display 203, the operator confirms the positions of the subject's tumor, heart as a blood pool, and muscles from the superimposed image, and performs an operation to set a region of interest within the tumor region, heart region, and muscle region in the image.

Next, the reception function 205b receives the setting of the regions of interest within the tumor region, heart region, and muscle region by the operator, and sends the received settings of the regions of interest (tumor region of interest, heart region of interest, and muscle region of interest) to the extraction function 205c (S2).

Here, the setting of the region of interest does not necessarily have to be performed manually, but may also be performed automatically. For example, the contours of structures in the image can be extracted using a known segmentation process, and the region of interest can be set in the image based on the position and shape of the extracted contour.

Next, the extraction function 205c extracts the average radioactivity values within the set tumor region of interest, heart region of interest, and muscle region of interest from the PET image (S3).

Next, the calculation function 205d calculates a first ratio, which is the ratio of the average radioactivity in the tumor region of interest to the average radioactivity in the heart region of interest, and a second ratio, which is the ratio of the average radioactivity in the tumor region of interest to the average radioactivity in the muscle region of interest, from the average radioactivity in the extracted tumor region of interest, heart region of interest, and muscle region of interest (S4).

Next, the evaluation function 205e evaluates that the tumor has a tendency for [18F]5-FU to accumulate if both the calculated first ratio and second ratio are greater than a predetermined threshold, and evaluates that the tumor has no tendency for [18F]5-FU to accumulate if at least one of the calculated first ratio and second ratio is smaller than the predetermined threshold (S5). Note that the evaluation function 205e may evaluate that the tumor has a moderate tendency for [18F]5-FU to accumulate if either one of the first ratio and the second ratio is smaller than the predetermined threshold, and may evaluate that the tumor has no tendency for [18F]5-FU to accumulate if both the first ratio and the second ratio are smaller than the predetermined threshold.

Then, a doctor can refer to the evaluation results obtained by the analysis device 200 and decide whether to apply 5-FU treatment or a treatment other than 5-FU treatment to the subject being evaluated.

Thus, in the embodiment, a first ratio, which is the ratio of the radioactivity value in the tumor region to the radioactivity value in the heart region, and a second ratio, which is the ratio of the radioactivity value in the tumor region to the radioactivity value in the muscle region, are calculated from the radioactivity values in the tumor region, heart region, and muscle region extracted from a PET image of a subject having a tumor to which [18F]5-FU has been administered, and the specificity of the accumulation of [18F]5-FU in the tumor is evaluated from the calculated first and second ratios. Therefore, according to the embodiment, it is possible to evaluate the comprehensive pharmacokinetics of 5-FU and the efficacy of 5-FU without imposing a burden on the patient.

More specifically, according to the embodiment, it is possible to evaluate the accumulation of 5-FU in a tumor without placing a burden on the patient. Furthermore, according to the embodiment, it is possible to prevent administration to patients who are not expected to benefit from 5-FU treatment, and in turn, it is possible to prevent the occurrence of side effects. Furthermore, according to the embodiment, it is possible to easily evaluate changes in the pharmacokinetics of 5-FU caused by the acquisition of resistance to 5-FU due to continuous administration of 5-FU. Furthermore, according to the embodiment, it is possible to prevent the progression of cancer associated with continuous administration of 5-FU to patients who are not expected to benefit from 5-FU treatment. Furthermore, according to the embodiment, it is possible to contribute to the decision to switch to an appropriate anticancer drug.

Although an embodiment of the present invention has been described, this embodiment is presented as an example and is not intended to limit the scope of the invention. This embodiment can be implemented in various other forms, and various omissions, substitutions, and modifications can be made without departing from the gist of the invention. This embodiment and its variations are within the scope of the invention and its equivalents as described in the claims, as well as the scope and gist of the invention.

Example 1 Visualization of the Pharmacokinetics of 5-FU Using [18F]5-FU The following experiments in steps 11 to 15 were carried out on DLD-1 mice (N=8) and DLD-1/5-FU mice (N=8) to attempt visualization of the pharmacokinetics of 5-FU using [18F]5-FU.

Here, the DLD-1 mouse is a cancer-bearing mouse having a tumor (average tumor volume 107 mm ³ ) derived from the colon cancer cell line DLD-1. The DLD-1/5-FU mouse is a cancer-bearing mouse having a tumor (average tumor volume 86 mm ³ ) derived from the colon cancer cell line DLD-1/5-FU. DLD-1/5-FU was established by culturing DLD-1 in a medium containing 5-FU. The sensitivity of DLD-1 and DLD-1/5-FU to 5-FU differs, with DLD-1 being sensitive to 5-FU and DLD-1/5-FU being resistant to 5-FU.

[Procedure 11] Mice are simultaneously administered 18 MBq of [18F]5-FU per mouse (see Figure 3) and 10 mg/kg of gimeracil (a 5-FU degrading enzyme inhibitor) per mouse via tail vein injection. Note that a dose of 18 MBq of [18F]5-FU is equivalent to a dose of 1.5 pg/kg of 5-FU.

[Step 12] Approximately 45 minutes after administration, the mouse is anesthetized and secured to the imaging stage.

[Step 13] 50 minutes after administration, the mouse is imaged for 10 minutes using a static scan with a PET device (Canon Medical Systems Corporation).

[Step 14] After imaging with the PET device, the imaging stage with the mouse fixed thereon is moved to an X-ray CT device (manufactured by Canon Medical Systems Corporation), and the mouse is imaged with the X-ray CT device.

[Step 15] PET imaging is performed using a medical image analysis viewer (software) that is installed in a computer connected to the PET device and the X-ray CT device and that is capable of setting the region of interest and extracting the average radioactivity value (%ID/g and SUV (Standardized Uptake Value)) within the region of interest. Specifically, the mouse weight, the dose of [18F]5-FU, the administration time, and the imaging start time are input on a specific operation screen provided by the viewer and displayed on the computer display, and the image contrast is set to the range of 0.5 to 2.0%ID/g wt, and PET imaging is performed.

An example of a PET image obtained from the experiment is shown in Figure 4. The image shown in Figure 4 (a) is a PET image of a DLD-1 mouse, and the image shown in Figure 4 (b) is a PET image of a DLD-1/5-FU mouse. In the figure, the circled area corresponds to the tumor area. The PET images made it possible to visualize a clear difference in the amount of [18F] accumulation between DLD-1-derived tumors and DLD-1/5-FU-derived tumors.

Example 2 Evaluation of Specificity of Accumulation of [18F]5-FU in Tumors In Example 1, the accumulation of [18F] was confirmed from PET images only in the DLD-1-derived tumors.

However, the amount of [18F] retained in the whole body of a mouse may differ between individuals. For example, in an individual with high accumulation of [18F] throughout the whole body, the tumor may be highlighted overall in the PET image, making it impossible to determine from the PET image whether or not there is specific accumulation of [18F] in the tumor. Conversely, in an individual with low accumulation of [18F] throughout the whole body, it is impossible to determine whether there is actually no accumulation of [18F] in the tumor, or whether the absolute amount of accumulation of [18F] is so small that it is not highlighted in the PET image.

Therefore, it is considered necessary to quantify the radioactivity at the tumor site from PET images and compare the quantified radioactivity between individuals.

However, because the amount of radioactivity retained throughout the body varies from individual to individual, it is not appropriate to compare only the amount of radioactivity accumulated in tumors between individuals.

Therefore, in Example 2, the ratio of radioactivity in the tumor to the radioactivity in the heart (hereafter referred to as the "tumor-blood ratio") and the ratio of radioactivity in the tumor to the radioactivity in the muscle (hereafter referred to as the "tumor-muscle ratio") were calculated using the radioactivity in the heart as the blood pool and the muscle as the standard, and the calculated tumor-blood ratios and tumor-muscle ratios were compared between individuals to relatively evaluate the specificity of the accumulation of [18F] in the tumor.

The tumor-blood ratio and tumor-muscle ratio for each mouse used in Example 1 were calculated according to steps 21 to 24 below, and from the calculated tumor-blood ratio and tumor-muscle ratio for each mouse, the average tumor-blood ratio and average tumor-muscle ratio for DLD-1 mice and the average tumor-blood ratio and average tumor-muscle ratio for DLD-1/5-FU mice were calculated.

[Step 21] Use the viewer to generate a superimposed image of the mouse's PET and CT images.

[Step 22] Identify the tumor, heart, and muscle regions while observing the overlaid image (see Figure 5).

[Step 23] On a specific operation screen provided by the viewer, set a region of interest within each identified region, and use the viewer to extract the average radioactivity value within each region of interest.

[Step 24] Calculate the tumor-blood ratio and tumor-muscle ratio from the average radioactivity value within each extracted region of interest.

The specificity of [18F] accumulation in tumors was evaluated from the calculated average tumor-blood ratio and average tumor-muscle ratio for DLD-1 and DLD-1/5-FU mice. The average tumor-blood ratio was 1.07 for DLD-1/5-FU mice, whereas the average tumor-muscle ratio was 1.99 for DLD-1 mice, which was significantly higher (p<0.01). The average tumor-muscle ratio was 2.14 for DLD-1 mice, whereas the average tumor-blood ratio was 1.08 for DLD-1/5-FU mice, which was significantly higher (p<0.01). In other words, the average tumor-blood ratio for DLD-1 mice was approximately 1.86 times higher than that for DLD-1/5-FU mice, and the average tumor-muscle ratio was approximately 1.98 times higher than that for DLD-1/5-FU mice, both of which were significantly higher.

Furthermore, to verify the validity of the comparison results of the tumor-blood ratio and tumor-muscle ratio obtained from the PET images, the radioactivity value of the tumor, the tumor-blood ratio, and the tumor-muscle ratio obtained from the tissue obtained at autopsy were compared. Specifically, four DLD-1 mice and four DLD-1/5-FU mice were prepared at each time point of 10 minutes, 30 minutes, 60 minutes, and 240 minutes after administration, and the following experiments in steps 31 to 34 were performed for each mouse to quantitatively compare the tumor radioactivity value between DLD-1 mice and DLD-1/5-FU mice, as well as the tumor-blood ratio and tumor-muscle ratio between DLD-1 mice and DLD-1/5-FU mice. Note that when obtaining the tumor-blood ratio from the tissue obtained at autopsy, the radioactivity in the actually collected blood was used as the standard, not the radioactivity in the heart, so the tumor-blood ratio obtained from the tissue obtained at autopsy is the ratio of the radioactivity in the tumor to the radioactivity in the blood.

[Procedure 31] Mice are simultaneously administered 1.8 MBq of [18F]5-FU per mouse and 10 mg/kg of gimeracil per mouse via tail vein injection.

[Step 32] After the time point has elapsed, the mouse is promptly dissected and the distribution of radioactivity in each tissue (tumor, blood, muscle, lung, bone, etc.) is analyzed. Specifically, the mouse is dissected, each tissue is separated from the mouse, and the weight of each separated tissue and the radioactivity level contained in each separated tissue are promptly measured.

[Step 33] Calculate the radioactivity value per unit weight of each tissue from the measured weight of each tissue and the radioactivity value contained in each tissue.

[Step 34] Calculate the tumor-blood ratio and tumor-muscle ratio from the calculated tumor radioactivity, blood radioactivity, and muscle radioactivity values.

As a result of the comparison, the average amount of [18F] accumulated (%ID/g) in DLD-1 mice was 2.0 times higher than that in DLD-1/5-FU mice (see the point corresponding to 60 minutes after administration in the line graph in Figure 6), the average tumor-blood ratio was 1.6 times higher (see the bar graph corresponding to the notation "60 min" in Figure 7), and the average tumor-muscle ratio was 1.9 times higher (see the bar graph corresponding to the notation "60 min" in Figure 7), all of which were significantly higher (p<0.01).

As shown in Figure 6, the accumulation in DLD-1 mice was higher than that in DLD-1/5-FU mice even at 10 minutes, 30 minutes, and 240 minutes after administration. More specifically, the accumulation in DLD-1 mice was not significantly different from that in DLD-1/5-FU mice at 10 minutes and 240 minutes after administration, but at 30 minutes after administration, the accumulation in DLD-1 mice was significantly higher than that in DLD-1/5-FU mice (p<0.01). In addition, as shown in Figures 7 and 8, the tumor-blood ratio and tumor-muscle ratio in DLD-1 mice were higher than those in DLD-1/5-FU mice even at 10 minutes, 30 minutes, and 240 minutes after administration. More specifically, 10 minutes and 240 minutes after administration, the tumor-blood ratio and tumor-muscle ratio of DLD-1 mice were not significantly different from those of DLD-1/5-FU mice, but 30 minutes after administration, the tumor-blood ratio and tumor-muscle ratio of DLD-1 mice were significantly higher than those of DLD-1/5-FU mice (p<0.01).

In Examples 1 and 2, a correlation was observed in the comparison results between the distribution of radioactivity in tissues obtained from PET images and the actual distribution of radioactivity in tissues, making it clear that it is possible to visualize the pharmacokinetics of 5-FU using [18F]5-FU and to evaluate the specificity of accumulation of [18F]5-FU in tumors in mice.

REFERENCE SIGNS LIST 10 Medical image diagnostic system 100 Medical image diagnostic device 200 Analysis device 201 Network interface 202 Input interface 203 Display 204 Memory circuit 205 Processing circuit 205a Display control function 205b Reception function 205c Extraction function 205d Calculation function 205e Evaluation function 300 Network

Claims (7)

An acquisition unit that acquires CT images and nuclear medicine images of a subject to which a radioactively labeled anticancer drug that is effective by accumulating in a tumor has been administered;
a receiving unit that receives a setting of a region of interest that specifies a tumor region, a blood region, and a muscle region based on the CT image;
an extracting unit that extracts detection values in a tumor region, a blood region, and a muscle region from the nuclear medicine image based on the set region of interest ;
a calculation unit that calculates a first comparison value that is a comparison result between the detection value in the blood region and the detection value in the tumor region, and a second comparison value that is a comparison result between the detection value in the muscle region and the detection value in the tumor region;
an evaluation unit that performs a first determination as to whether or not a condition related to the first comparison value is satisfied, and performs a second determination as to whether or not a condition related to the second comparison value is satisfied , and evaluates the accumulation of the drug in a tumor based on a combination of the first determination and the second determination ;
An analysis device comprising: The analysis device according to claim 1, wherein the first comparison value is a ratio between the detection value in the blood region and the detection value in the tumor region. The analysis device according to claim 1, wherein the second comparison value is a ratio between the detection value in the muscle region and the detection value in the tumor region. On the computer,
An acquisition function for acquiring CT images and nuclear medicine images of a subject to which a radioactively labeled anticancer drug that is effective by accumulating in a tumor has been administered;
A reception function for receiving settings of a region of interest that specifies a tumor region, a blood region, and a muscle region based on the CT image;
an extraction function for extracting detection values in a tumor region, a blood region, and a muscle region from the nuclear medicine image based on the set region of interest ;
a calculation function for calculating a first comparison value which is a comparison result between the detection value in the blood region and the detection value in the tumor region, and a second comparison value which is a comparison result between the detection value in the muscle region and the detection value in the tumor region;
an evaluation function of making a first determination as to whether or not a condition related to the first comparison value is satisfied, and making a second determination as to whether or not a condition related to the second comparison value is satisfied , and evaluating the accumulation of the drug in the tumor based on a combination of the first determination and the second determination ;
An analysis program to achieve this. The analysis device according to any one of claims 1 to 3, wherein the evaluation unit evaluates the accumulation of the drug in the tumor in three or more stages based on a combination of the first determination and the second determination. The analysis device according to any one of claims 1 to 3 and 5, wherein the reception unit receives from an operator an operation to set the region of interest in a superimposed image of the CT image and the nuclear medicine image displayed on the display unit. 6. The analysis device according to claim 1, wherein the reception unit receives the setting of the region of interest based on a segmentation process performed on the CT image.

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