Table 2 Preclinical and clinical studies on in vivo monitoring and imaging of measles virus (MV) infection, replication, and expression
From: Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?
Study/year | Imaging technique | Tumor type | Data sources | Genes/protein | Route | Protein targeting drug | Main results |
|---|---|---|---|---|---|---|---|
Deyle et al./2015 [55] | SPECT/CT | Malignant peripheral nerve sheath | Athymic nude mice | hNIS | IT | 125I | MV localization and distribution could be monitored by imaging of I-125 uptake |
Dingli et al./2004 [56] | Gamma camera | Myeloma | Mice | hNIS | IV | 123I | In vivo replication of MV-NIS peaked 9Â days after virus injection |
Galanis et l./2015 [58] | SPECT/CT | Ovarian cancer | Human | hNIS | IP | 123I | No dose-limiting toxicity was observed in 16 patients treated at the 108–109 TCID50 dose level; all observed toxicities were grade 1 and 2 |
Hasegawa et al./2006 [75] | Gamma camera and bioluminescence | Ovarian cancer | Mice | hNIS; blood CEA | IT, IV | Tc-99Â m sodium pertechnetate; luciferase (Fluc) and bhCG | Viral gene expression was monitored by measuring blood CEA levels, and the location of virus-infected cells was monitored by gamma camera imaging; The gamma camera scans were significantly less sensitive than the plasma CEA marker for monitoring virus infection |
Hutzen et al./2012 [65] | Bioluminescent (Cherenkov) imaging | Medulloblastoma | Mice | hNIS | IT | D-Luciferin | The MV-NIS mouse indicated an increased bioluminescent signal originating from the tumor that 131I had accumulated |
Msaouel et al./2009 [64] | Gamma camera | Prostate | Nude mice | hNIS | IT, IV | 123I | In vivo replication of MV-NIS depends on the administration route. Strong positive tumor 123I uptake is seen 4Â days after IT administration of MV-NIS, and 14Â days after IV administration of MV-NIS. Persistent transgene expression can be detected for as long as 36Â days after IV administration of the virus |
Myers et al./2007 [19] | – | Myeloma | SCID mice, squirrel monkey | hNIS | IV | 123I | No adverse effect was observed |
Opyrchal et al./2012 [67] | Gamma camera | Glioblastoma | BALB/c nude mice | hNIS | IT | 123I; Tc-99Â m sodium pertechnetate | Tumor uptake of radioisotope in MV-NIS-treated mice was increased; peak at day 3 and persistence at 20Â days after viral administration. Expression of NIS protein in infected cells results in the effective concentration of radioactive iodine that allows for in vivo monitoring of localization of MV-NIS infection by measuring uptake of I-123 and Tc-99Â m |
Penheiter et al./2012 [62] | SPECT/CT | Pancreatic | Nude mice | hNIS | IT, IV | 123I | Pinhole micro-SPECT/CT imaging using the NIS reporter allows for precise localization and quantitation of oncolytic MV-NIS infection. This method can replace autoradiography and Immunohistochemistry analysis |
Penheiter et al./2012 [77] | SPECT/CT | Pancreatic | Nude mice | hNIS | IT | Tc-99Â m sodium pertechnetate | IT viral delivery can be monitored using image-guided injection techniques |
Penheiter et al./2010 [59] | SPECT/CT | Pancreatic | Nude mice | hNIS | IT | 123I | Delivery of 131I radiotherapy to NIS-expressing tumors can be optimized using micro-SPECT/CT imaging guidance. In vivo viral replication was variable among mice (peak between 2Â days and 6Â days following viral administration, and undetectable at 9Â days after viral injection) |
Reddi et al./2012 [73] | SPECT/CT | Anaplastic thyroid | Nude mice | hNIS | IT | Tc-99Â m sodium pertechnetate | NIS expression peaked at day 3 and was persistence up to day 22 following viral administration |
Russell et al./2014 [60] | SPECT/CT | Myeloma and plasmacytoma | Human | hNIS | IV | 123I | In all the two patients, tumor imaging was clearly documented. The size of the lesions was variable in hNIS mediated radioiodine SPECT-CT for the same lesions shown in the imaging in comparison with the normal FDG PET-CT. In vivo viral replication depends on patient and plasmacytoma. Radioiodine uptake returned to the background at day 28 following MV-NIS administration |
Carlson et al./2009 [61] | Gamma camera, SPECT/CT | Pancreatic | Nude mice | hNIS | IT | 123I | Mice infected with MV-NIS concentrated radioiodine, that allows for serial quantitative imaging with 123I micro-SPECT/CT. The peak iodide uptake was 2Â days after MV-NIS administration |
Dispenzieri et al./2017 [57] | SPECT/CT | Multiple myeloma | Human | hNIS | IV | 123I | 8 out of the 31 patients had some degree of 123I uptake on their SPECT/CT scans |
Miest et al./2013 [72] | SPECT/CT | Mantle cell lymphoma | SCID mice | hNIS | IT, IV | Tc-99Â m sodium pertechnetate | NIS gene results in concentrating iodide within infected cells, allowing non-invasive imaging. High-resolution imaging visualized the spread of infections in primary and metastatic tumors for over 2Â weeks after treatment, documenting homogeneous virus seeding and spread restricted to perfused tissue |
Jung et al./2018 [78] | SPECT/CT | Pancreatic | Nude mice | hNIS | IT | Tc-99Â m | In vivo radioisotope uptake was significantly correlated with viral N and NIS gene expression |
Kemler et al./2019 [63] | Intravital imaging | Fibrosarcoma | Athymic nude mice | Blue fluorescent protein containing the nuclear localization sequence | – | – | Intravital imaging system using the dorsal skin fold chamber allows for serial, non-invasive imaging of tumor cells and replication of a fusogenic and a hypofusogenic MV. There were distinctly different replication kinetics and phenotypes of these two viruses |
Li et al./2012 [66] | SPECT/CT | Squamous cell carcinoma | Athymic nude mice | hNIS | IT | 125I | In vivo viral replication peak occurred 3Â days after viral administration |