The Functional Imaging Division actively investigated for the whole of 2007 as well as 2008 two kinds of imaging modalities, namely, radionuclide imaging and magnetic resonance imaging.
18-Fluorodeoxyglucose positron emission tomography (FDG PET) is a useful tool for detecting malignant lesions. In particular, the accurate diagnosis of regional lymph node (LN) metastases is important to be able to select the optimal treatment for malignancy. However, the results of conventional anatomical imaging tests such as computed tomography (CT) and magnetic resonance imaging (MRI) are not sufficiently accurate. To overcome this problem, we are currently and actively applying FDG PET/CT tests to the diagnosis of LN metastases from colorectal malignancies (65). Notably, the results of FDG PET/CT tests can vary depending on the acquisition conditions and image processing, especially in the diagnosis of small lesions such as LN metastases. Our investigation revealed that the optimization of the iteration number in the ordered-subset expectation-maximization reconstruction algorithm enhanced the contrast of LN metastases from colorectal cancer, and that the diagnostic accuracy of LN metastases was improved (136). The statistical processing of the reconstructed images to indicate the regions suspected of having LN metastases also played a supplementary role in the diagnosis of LN metastases (137).
In cancer therapy, the ratio of non-surgical treatment is progressively increasing. More specifically, in chemotherapy, many molecular targeted agents are being introduced in clinical practice. Response Evaluation Criteria In Solid Tumors, which is one of the most commonly used criteria for evaluating therapeutic effects, is based on morphological changes; however, this criterion presents many problems for evaluating therapy when using molecular targeted agents (138). An FDG PET test is expected to contribute to the evaluation of the effects of such non-surgical treatments. In the current radiotherapy approaches such as stereotactic methods, unique morphological changes not observed in conventional radiotherapy appear after treatment. In such cases, FDG PET tests would be useful for evaluating therapeutic effects (139).
The NanoSPECT/CT scanner, which is a combined scanner of the SPECT and CT systems dedicated for small animal imaging, has the potential to clearly visualize the distribution of radioactive compounds in mice in vivo. However, our evaluation of the performance of this scanner revealed that approximately 0.5 MBq/g of radionuclides must be accumulated in the target tissues to clearly visualize their heterogeneous distribution. Moreover, radiopharmaceuticals with high specific radioactivity must be injected in large amounts in mice. In this regard, liposomes can be good candidate carriers of large amounts of radionuclides. We obtained radioactive liposomes with high specific radioactivity of In-111 and Tc-99m by the active loading method. By using Tc-99m-labeled liposomes, radioactivity by as much as 70 MBq could be injected into mice.
With regard to tissue contrast, MRI can provide more useful images than CT. However, a combined scanner of the SPECT and MRI systems is not yet commercially available because of the strong magnetic field produced by MRI. Therefore, we obtained a fusion image of SPECT and MRI using a common bed capable of rigidly fixing the scanned area. Good SPECT and MRI fusion images of the mouse brain and sentinel lymph node (SLN) in the popliteal region were obtained.
In addition, the planer positron imaging system is a convenient tool for visualizing the distribution of positron emitters in vivo. This system was installed into a proton beam therapy unit at our institute, and it is presently being used for evaluating an irradiated area in vivo in proton beam therapy (162).
MRI can visualize various kinds of cancer lesions by utilizing contrast given by some tissue parameters including relaxation times and apparent diffusion coefficients. We are currently using a 3 Tesla whole-body MRI scanner equipped with high-sensitive receiver coils. This year, we have developed a new type of receiver coil for small animal imaging. An increase of approximately 20% in the signal-to-noise ratio was achieved using this coil. Since the coil is fully compatible with the common bed mentioned above, it greatly facilitates the precise co-registering of anatomical MR images with an in-plane resolution of < 100 x 100 μm2 with functional SPECT images.
Taking advantage of this newly developed equipment, we are continuously exerting great efforts to develop new techniques for the precise diagnosis of cancer lesions and for the accurate evaluation of the effectiveness of some cancer treatment strategies currently available in clinic. As our first MR research topic, we investigated superparamagnetic iron oxide (SPIO) enhanced MRI for the visualization of ablated hepatic tissue after radiofrequency ablation (RFA) treatment. We used this MRI technique in a rabbit model and found that the hepatic parenchyma after RFA treatment showed darker signals than that in untreated areas. We therefore believe that SPIO-enhanced MRI can precisely visualize ablative margins in human hepatoma cases. The precise diagnosis of ablative margins is considered very helpful for assessing the risks of marginal recurrence and for predicting patient prognosis. For our second MR research topic, we investigated manganese-enhanced MRI (MEMRI) for the visualization of pancreatic cancer xenografts grown in the sciatic nerve of mice. Manganese ions are well-known T1 contrast agents. After intraneural administration, these ions are taken up by neurons via the calcium channel and are transported via axonal flow. We succeeded for the first time in visualizing the sciatic nerve of mice, which is approximately 1 mm in diameter, involved in human pancreatic cancer cell growth on in vivo MEMRI. Therefore, MEMRI may be useful for diagnosing the perineural extension of pancreatic cancer by demonstrating the functional difference in the manganese transport system between the involved nerves and the intact nerves. Nevertheless, further investigation is needed to determine the optimal drug design and administration dose that is safe for humans.
SLN is a LN that directly receives the lymphatic flow from the primary lesion of malignancy. It is reported that LN metastases firstly appear in SLN in breast cancer and malignant melanoma. Many recent studies have suggested the possibility that this concept would be more widely applied to other malignancies. The study using Tc-99m phytate has suggested the feasibility of SLN navigation surgery for the treatment of the early stage of hypopharyngeal cancer and laryngeal cancer (141). We encountered a patient with laryngeal cancer whose SLN was located in the contralateral side of the neck relative to the primary tumor, and metastasis was found only in this SLN. The SLN concept can also be likely applied to gastric cancer if tumor invasion is limited to the submucosal layer. Since salvage treatment is difficult in recurrent gastric cancer, curability must be taken into consideration in its treatment. Therefore, SLN navigation surgery for gastric cancer should be performed based on the concept of the lymphatic basin. In the identification of the lymphatic basin of gastric cancer, lymphoscintigraphy with Tc-99m-labeled radiocolloids was proven useful (140).
● H. Fujii ●
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