• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.12
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• pp.637-643
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• 2018

Radioimmunotherapy (RIT) is a therapy that takes advantage of the "cross-fire" effect of emitted radiation by radionuclides conjugated to tumor-directed monoclonal antibodies (mAb) (including those fragments) or peptides. While RIT has been successfully employed for the treatment of lymphoma, mostly with radiolabeled antibodies against CD20 [$^{90}yttrium$ ($^{90}Y$)-ibritumomab tiuxetan; $Zevalin^{(R)}$ and $^{131}iodine$ ($^{131}I)-tositumomab$; $Bexxar^{(R)}$], its use in solid tumors is more challenging, so far. Immuno-PET, a tool for tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and guide mAb-based therapy. RIT in solid tumors including head and neck cancer may be an alternative treatment with advances in various biological, chemical, and treatment procedures, and it may help to reduce unnecessary exposure and enhance the therapeutic efficacy. Also, immuno-PET based on RIT might play an important role in cancer staging, in patients or targets selection of targeted therapeutics and in monitoring the response of targeted therapeutics as precision medicine. In this review, fundamentals of RIT/immune-PET and current knowledge of the preclinical/clinical trials in RIT for solid tumor including head and neck cancer are reviewed.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.60-71
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• 2009

Purpose: We assessed the absorbed dose to the tumor ($Dose_{tumor}$) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with $^{131}I$ rituximab for NHL. Materials and Methods: Patients with NHL (n=4) were administered a therapeutic dose of $^{131}I$ rituximab. Serial WB planar images alter RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROls were drawn on the region of tumor (n=7) and left medial thigh as background, and $Dose_{tumor}$ was calculated. The correlation between $Dose_{tumor}$ and the CT-based tumor volume change alter RIT was analyzed. The differences of $Dose_{tumor}$ and the tumor volume change according to the number of RIT were also assessed. Results: The values of absorbed dose were $397.7{\pm}646.2cGy$ ($53.0{\sim}2853.0cGy$). The values of CT-based tumor volume were $11.3{\pm}9.1\;cc$ ($2.9{\sim}34.2cc$), and the % changes of tumor volume before and alter RIT were $-29.8{\pm}44.3%$ ($-100.0%{\sim}+42.5%$), respectively. $Dose_{tumor}$ and the tumor volume change did not show the linear relationship (p>0.05). $Dose_{tumor}$ and the tumor volume change did not correlate with the number of repeated administration (p>0.05). Conclusion: We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.941-945
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• 2015

Semaphoring is a transmembrane receptor which participates in many cytokine-mediated signal pathways that are closely related to the angiogenesis, occurrence and development of carcinoma. The present study was designed to access the effect of mono-antibody (mAb) guided radioimmunotherapy (RIT) on skin carcinoma and investigate the potential mechanisms. Semaphoring mAb was acquired from mice (Balb/c), purified with rProtein A column; purity, concentration and activity were tested with SDS-PAGE and indirect ELISA; specificity and expression on the cutanuem carcinoma line and tissue were tested by Western blotting; morphology change was assessed by microscopy. MTT assay and colony inhibition tests were carried out to test the influence on the proliferation of tumor cells; Western blotting was also carried out for expression of apoptosis-associated (caspase-3, Bax, Bcl-2) and proliferation-related (PI3K, p-Akt, Akt, p-ERK1/2, ERK1/2) proteins and analyse the change in signal pathways (PI3K/Akt and MEK/ERK). The purity of purified semaphorin mAb was 96.5% and the titer is about $1{\times}10^6$. Western blotting showed semaphoring mAb to have specifically binding stripes with semaphoring b1b2 protein, B16F10, and A431 cells at 39KDa, 100KDa and 130KDa, respectively. Positive expression was detected both in cutanuem carcinoma line and tissue and it mostly located in cell membranes. MMT assay revealed dose-relate and time-relate inhibitory effect of semaphorin mAb on A431 and B16F10. Colony inhibition tests also showed dose-relate inhibitory effects. Western blotting demonstrated the expression of apoptosis and proliferation-related protein and changes in signal pathway. In conclusion, we demonstrated that semaphorin is highly expressed on the tumor cell-surfaces and RIT with semaphorin mAb has effect in i nhibiting proliferation and accelerating apoptosis of tumor cells.

• Biomedical Science Letters
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• v.21 no.1
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• pp.23-31
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• 2015

Recently, specific antibodies have been used extensively to diagnose and treat various diseases. It is essential to assess the efficacy and specificity of antibodies, especially the in vivo environment. Anti-HER-2/neu mAb was evaluated as a possible transporting agent for radioimmunotherapy. The monoclonal antibody was successfully radio-labeled with $^{131}I$. In vitro binding assays were performed to confirm its targeting ability using another radio-iodine, $^{125}I$. Binding percentage of $^{125}I$ labeled anti-HER-2/neu mAb in HER-2/neu expressing CT-26 cells was found to be 4.5%, whereas the binding percentage of $^{125}I$ labeled anti-HER-2/neu mAb in wild-type CT-26 was only 0.45%. In vivo images were obtained and analyzed through $\gamma$-camera and an optical fluorescent modality, IVIS-200. $\gamma$-camera images showed that $^{131}I$ labeled anti-HER-2/neu mAb accumulated in HER-2/neu CT-26 tumors. Optical imaging based on near infrared fluorescence labeled anti-HER-2/neu mAb showed higher fluorescence intensities in HER-2/neu CT-26 tumors than in wild-type CT-26 tumors. Anti-HER-2/neu mAb was found to specifically bind to its receptor expressing tumor. Our study demonstrates that in vivo imaging technique is a useful method for the evaluation of an antibody's therapeutic and diagnostic potentials.