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PloS One 2019Hypoxia can induce radiation resistance and is an independent prognostic marker for outcome in head and neck cancer. As 18F-FMISO (FMISO), a hypoxia tracer for PET, is... (Comparative Study)
Comparative Study
BACKGROUND
Hypoxia can induce radiation resistance and is an independent prognostic marker for outcome in head and neck cancer. As 18F-FMISO (FMISO), a hypoxia tracer for PET, is far less common than 18F-FDG (FDG) and two separate PET scans result in doubled cost and radiation exposure to the patient, we aimed to predict hypoxia from FDG PET with new techniques of voxel based analysis and texture analysis.
METHODS
Thirty-eight patients with head-and-neck cancer underwent consecutive FDG and FMISO PET scans before any treatment. ROIs enclosing the primary cancer were compared in a voxel-by-voxel manner between FDG and FMISO PET. Tumour hypoxia was defined as the volume with a tumour-to-muscle ratio (TMR) > 1.25 in the FMISO PET and hypermetabolic volume was defined as >50% SUVmax in the FDG PET. The concordance rate was defined as percentage of voxels within the tumour which were both hypermetabolic and hypoxic. 38 different texture analysis (TA) parameters were computed based on the ROIs and correlated with presence of hypoxia.
RESULTS
Within the hypoxic tumour regions, the FDG uptake was twice as high as in the non-hypoxic tumour regions (SUVmean 10.9 vs. 5.4; p<0.001). A moderate correlation between FDG and FMISO uptake was found by a voxel-by-voxel comparison (r = 0.664 p<0.001). The average concordance rate was 25% (± 22%). Entropy was the TA parameter showing the highest correlation with hypoxia (r = 0.524 p<0.001).
CONCLUSION
FDG uptake was higher in hypoxic tumour regions than in non-hypoxic regions as expected by tumour biology. A moderate correlation between FDG and FMISO PET was found by voxel-based analysis. TA yielded similar results in FDG and FMISO PET. However, it may not be possible to predict tumour hypoxia even with the help of texture analysis.
Topics: Adult; Aged; Aged, 80 and over; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Head and Neck Neoplasms; Humans; Male; Middle Aged; Misonidazole; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Radiation Tolerance; Radiopharmaceuticals; Tumor Hypoxia
PubMed: 30818360
DOI: 10.1371/journal.pone.0213111 -
Radiology. Imaging Cancer May 2022Purpose To determine the variance and correlation with tumor viability of fluorine 18 (F) fluoromisonidazole (FMISO) uptake in hepatocellular carcinoma (HCC) prior to...
Limitations of Fluorine 18 Fluoromisonidazole in Assessing Treatment-induced Tissue Hypoxia after Transcatheter Arterial Embolization of Hepatocellular Carcinoma: A Prospective Pilot Study.
Purpose To determine the variance and correlation with tumor viability of fluorine 18 (F) fluoromisonidazole (FMISO) uptake in hepatocellular carcinoma (HCC) prior to and after embolization treatment. Materials and Methods In this single-arm, single-center, prospective pilot study between September 2016 and March 2017, participants with at least one tumor measuring 1.5 cm or larger with imaging or histologic findings diagnostic for HCC were enrolled (five men; mean age, 68 years; age range, 61-76 years). Participants underwent F-FMISO PET/CT before and after bland embolization of HCC. A tumor-to-liver ratio (TLR) was calculated by using standardized uptake values of tumor and liver. The difference in mean TLR before and after treatment was compared by using a Wilcoxon rank sum test, and correlation between TLR and tumor viability was assessed by using the Spearman rank correlation coefficient. Results Four participants with five tumors were included in the final analysis. The median tumor diameter was 3.2 cm (IQR, 3.0-3.9 cm). The median TLR before treatment was 0.97 (IQR, 0.88-0.98), with a variance of 0.02, and the median TLR after treatment was 0.85 (IQR, 0.79-1), with a variance of 0.01; both findings indicate a narrow range of F-FMISO uptake in HCC. The Spearman rank correlation coefficient was 0.87, indicating a high correlation between change in TLR and nonviable tumor. Conclusion Although there was a correlation between change in TLR and response to treatment, the low signal-to-noise ratio of F-FMISO in the liver limited its use in HCC. Molecular Imaging-Clinical Translation, Embolization, Abdomen/Gastrointestinal, Liver Clinical trial registration no. NCT02695628 © RSNA, 2022.
Topics: Aged; Carcinoma, Hepatocellular; Embolization, Therapeutic; Fluorine; Humans; Hypoxia; Liver Neoplasms; Male; Middle Aged; Misonidazole; Pilot Projects; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals
PubMed: 35485937
DOI: 10.1148/rycan.210094 -
World Journal of Nuclear Medicine 2021The aim of this study was to correlate endogenous tissue biomarkers of hypoxia with quantitative imaging parameters derived from F-fluoro-misonidazole (F-MISO) and...
The aim of this study was to correlate endogenous tissue biomarkers of hypoxia with quantitative imaging parameters derived from F-fluoro-misonidazole (F-MISO) and F-fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) and clinical outcomes in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Tumor-tissue blocks of HNSCC patients with pretreatment F-MISO-PET/CT and FDG-PET/CT were de-archived for expression of hypoxia-inducible factor-1 alpha (HIF-1α) subunit, carbonic anhydrase-IX (CA-IX), and glucose transporter subunit-1 (GLUT-1) using immunohistochemistry (IHC). The intensity of staining was graded and correlated with quantitative imaging parameters and with disease-related outcomes. Tissue blocks were analyzed for 14 of 20 patients. On IHC, median H-scores for HIF-1α, CA-IX, and GLUT-1 were 130, 0, and 95, respectively. No significant correlation of tissue biomarkers of hypoxia with quantitative imaging parameters was found. However, borderline significant correlation was seen for H-scores of CA-IX with hypoxic tumor volume (HTV) ( = 0.873, = 0.054) and fractional hypoxic volume ( = 0.824, = 0.086) derived from F-MISO-PET/CT. At a median follow-up of 43 months, 5-year Kaplan-Meier estimates of locoregional control, disease-free survival, and overall survival were 53%, 43%, and 40%, respectively. Increased expression of HIF-1α or GLUT-1 (dichotomized by median H-scores) was not individually associated with disease-related outcomes. However, a combination of high HTV (>4.89cc) with above median H-scores of either HIF-1α (>130) and/or GLUT-1 (>95) was associated with worse clinical outcomes. None of the three patients with such "adverse hypoxic profile" were long-term survivors. There is no significant correlation of endogenous tissue biomarkers of hypoxia (HIF-1α, CA-IX, and GLUT-1) with quantitative imaging parameters (on F-MISO-PET/CT and FDG-PET/CT) or long-term outcomes in HNSCC. However, a combination of both can identify a subgroup of patients with adverse outcomes.
PubMed: 34703390
DOI: 10.4103/wjnm.WJNM_91_20 -
Physics in Medicine and Biology Dec 2016Positron emission tomography (PET) using F-fluoromisonidazole (FMISO) is a promising technique for imaging tumour hypoxia, and a potential target for radiotherapy...
Positron emission tomography (PET) using F-fluoromisonidazole (FMISO) is a promising technique for imaging tumour hypoxia, and a potential target for radiotherapy dose-painting. However, the relationship between FMISO uptake and oxygen partial pressure ([Formula: see text]) is yet to be quantified fully. Tissue oxygenation varies over distances much smaller than clinical PET resolution (<100 μm versus ∼4 mm), and cyclic variations in tumour perfusion have been observed on timescales shorter than typical FMISO PET studies (∼20 min versus a few hours). Furthermore, tracer uptake may be decreased in voxels containing some degree of necrosis. This work develops a computational model of FMISO uptake in millimetre-scale tumour regions. Coupled partial differential equations govern the evolution of oxygen and FMISO distributions, and a dynamic vascular source map represents temporal variations in perfusion. Local FMISO binding capacity is modulated by the necrotic fraction. Outputs include spatiotemporal maps of [Formula: see text] and tracer accumulation, enabling calculation of tissue-to-blood ratios (TBRs) and time-activity curves (TACs) as a function of mean tissue oxygenation. The model is characterised using experimental data, finding half-maximal FMISO binding at local [Formula: see text] of 1.4 mmHg (95% CI: 0.3-2.6 mmHg) and half-maximal necrosis at 1.2 mmHg (0.1-4.9 mmHg). Simulations predict a non-linear non-monotonic relationship between FMISO activity (4 hr post-injection) and mean tissue [Formula: see text] : tracer uptake rises sharply from negligible levels in avascular tissue, peaking at ∼5 mmHg and declining towards blood activity in well-oxygenated conditions. Greater temporal variation in perfusion increases peak TBRs (range 2.20-5.27) as a result of smaller predicted necrotic fraction, rather than fundamental differences in FMISO accumulation under acute hypoxia. Identical late FMISO uptake can occur in regions with differing [Formula: see text] and necrotic fraction, but simulated TACs indicate that additional early-phase information may allow discrimination of hypoxic and necrotic signals. We conclude that a robust approach to FMISO interpretation (and dose-painting prescription) is likely to be based on dynamic PET analysis.
Topics: Computer Simulation; Humans; Hypoxia; Misonidazole; Models, Theoretical; Necrosis; Neoplasms; Oxygen; Positron-Emission Tomography; Radiopharmaceuticals; Spheroids, Cellular
PubMed: 27880734
DOI: 10.1088/1361-6560/61/24/8596 -
Journal of Nuclear Medicine : Official... Oct 2021Conventional MRI plays a key role in the management of patients with high-grade glioma, but multiparametric MRI and PET tracers could provide further information to...
Simultaneous Mapping of Vasculature, Hypoxia, and Proliferation Using Dynamic Susceptibility Contrast MRI, F-FMISO PET, and F-FLT PET in Relation to Contrast Enhancement in Newly Diagnosed Glioblastoma.
Conventional MRI plays a key role in the management of patients with high-grade glioma, but multiparametric MRI and PET tracers could provide further information to better characterize tumor metabolism and heterogeneity by identifying regions having a high risk of recurrence. In this study, we focused on proliferation, hypervascularization, and hypoxia, all factors considered indicative of poor prognosis. They were assessed by measuring uptake of F-3'-deoxy-3'-F-fluorothymidine (F-FLT), relative cerebral blood volume (rCBV) maps, and uptake of F-fluoromisonidazole (F-FMISO), respectively. For each modality, the volumes and high-uptake subvolumes (hot spots) were semiautomatically segmented and compared with the contrast enhancement (CE) volume on T1-weighted gadolinium-enhanced (T1w-Gd) images, commonly used in the management of patients with glioblastoma. Dynamic susceptibility contrast-enhanced MRI (31 patients), F-FLT PET (20 patients), or F-FMISO PET (20 patients), for a total of 31 patients, was performed on preoperative glioblastoma patients. Volumes and hot spots were segmented on SUV maps for F-FLT PET (using the fuzzy locally adaptive bayesian algorithm) and F-FMISO PET (using a mean contralateral image + 3.3 SDs) and on rCBV maps (using a mean contralateral image + 1.96 SDs) for dynamic susceptibility contrast-enhanced MRI and overlaid on T1w-Gd images. For each modality, the percentages of the peripheral volumes and the peripheral hot spots outside the CE volume were calculated. All tumors showed highly proliferated, hypervascularized, and hypoxic regions. The images also showed pronounced heterogeneity of both tracers regarding their uptake and rCBV maps, within each individual patient. Overlaid volumes on T1w-Gd images showed that some proliferative, hypervascularized, and hypoxic regions extended beyond the CE volume but with marked differences between patients. The ranges of peripheral volume outside the CE volume were 1.6%-155.5%, 1.5%-89.5%, and 3.1%-78.0% for F-FLT, rCBV, and F-FMISO, respectively. All patients had hyperproliferative hot spots outside the CE volume, whereas hypervascularized and hypoxic hot spots were detected mainly within the enhancing region. Spatial analysis of multiparametric maps with segmented volumes and hot spots provides valuable information to optimize the management and treatment of patients with glioblastoma.
Topics: Adult; Glioblastoma; Humans; Middle Aged; Misonidazole; Positron-Emission Tomography
PubMed: 34016725
DOI: 10.2967/jnumed.120.249524 -
Journal of Nuclear Medicine : Official... Jul 2017Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric...
Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with F-fluoromisonidazole (F-FMISO) dynamic PET (dPET) in head and neck cancer. One hundred twenty head and neck cancer patients underwent 0- to 30-min F-FMISO dPET in a customized immobilization mask, followed by 10-min static acquisitions starting at 93 ± 6 and 160 ± 13 min after injection. A total of 248 lesions (≥2 cm) were analyzed. Voxelwise pharmacokinetic modeling was conducted using an irreversible 1-plasma 2-tissue-compartment model to calculate surrogate biomarkers of tumor hypoxia (), perfusion (), and F-FMISO distribution volume. The analysis was repeated with truncated dPET datasets. Substantial inter- and intratumor heterogeneity was observed for all investigated metrics. Equilibration between the blood and unbound F-FMISO was rapid in all tumors. F-FMISO distribution volume deviated from the expected value of unity, causing discrepancy between maps and total F-FMISO uptake and reducing the dynamic range of total F-FMISO uptake for quantifying the degree of hypoxia. Both positive and negative trends between hypoxia and perfusion were observed in individual lesions. All investigated metrics were reproducible when calculated from a truncated 20-min dataset. F-FMISO dPET provides the data necessary to generate parametric maps of tumor hypoxia, perfusion, and radiotracer distribution volume. These data clarify the ambiguity in interpreting F-FMISO uptake and improve the characterization of lesions. We show total acquisition times can be reduced to 20 min, facilitating the translation of F-FMISO dPET into the clinic.
Topics: Adult; Aged; Aged, 80 and over; Female; Head and Neck Neoplasms; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Misonidazole; Multimodal Imaging; Neovascularization, Pathologic; Observer Variation; Oxygen; Perfusion Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Tumor Hypoxia
PubMed: 28183993
DOI: 10.2967/jnumed.116.188649 -
Biomedicine & Pharmacotherapy =... Nov 2019The aim of this study was to evaluate the application of F-flortanidazole (F-HX4)/F-fluoromisonidazole (F-FMISO) - based micro positron emission tomography/computed...
OBJECTIVE
The aim of this study was to evaluate the application of F-flortanidazole (F-HX4)/F-fluoromisonidazole (F-FMISO) - based micro positron emission tomography/computed tomography (PET/CT) for imaging of tumor hypoxia and radiotherapy-associated changes in mice.
MATERIALS AND METHODS
Radiotracer-based cellular uptake was performed to explore the correlation between radiotracer uptake and hypoxia state in cells. Animal models were established using subcutaneous injection of the human breast cancer line (MDA-MB-231) in a nude mouse. The effect of radiotherapy on tumor xenograft was assessed by measuring the tumor volume and mouse survival time. Meanwhile, mice with xenograft were imaged with F-FMISO andF-HX4 PET/CT before and after radiotherapy. Tumor-to-normal muscle ratio (T/N) of F-FMISO andF-HX4 maximum uptake was calculated by selecting a region of interest. Changes in tumor biology were assessed with immunohistochemical staining; T/N (F-FMISO) and T/N (F-HX4) were analyzed in relation to tumor volume, survival time, and the expression of tumor biomarkers, including hypoxia-inducible factor (HIF)-1α, glucose transporter (Glut-1) and the proliferation antigen Ki67.
RESULTS
Higher tracer uptake (both F-FMISO and F-HX4) was observed in hypoxic cells compared to oxygenated cell. The in vivo study suggested that both T/N (F-FMISO) and T/N (F-HX4) were positively correlated with tumor hypoxia volume (p = 0.014 and p = 0.009, respectively), but negatively associated with survival time (p = 0.012 and p = 0.007, respectively). HIF-1α, Glut-1 and Ki67 expression in tumors were downregulated after radiotherapy. T/N (F-HX4) was correlated with the expression of hypoxia marker HIF-1α in xenografts (r = 0.768, p = 0.025); while T/N (F-FMISO) was moderately correlated with the expressions of Ki67 (r = 0.412, p = 0.041). No significant correlation was detected between Glut-1 expression and T/N (F-FMISO) or T/N (F-HX4) (r = 0.511, p = 0.097 and r=0.562, p = 0.126, respectively).
CONCLUSIONS
Both F-HX4 and F-FMISO PET/CT can be used as biomarkers for tumor hypoxia and radiotherapy-associated changes. The clinical utilization of these two PET tracers needs to be further validated.
Topics: Animals; Azoles; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Female; Fluorine Radioisotopes; Humans; Linear Models; Mice, Inbred BALB C; Mice, Nude; Misonidazole; Multivariate Analysis; Positron Emission Tomography Computed Tomography; Tomography, X-Ray Computed; Tumor Burden; Tumor Hypoxia; Xenograft Model Antitumor Assays
PubMed: 31526971
DOI: 10.1016/j.biopha.2019.109454 -
Molecular Oncology May 2016Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of...
BACKGROUND
Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with (18)F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib.
METHODS
Two patient-derived pancreas xenografts (PDXs; Panc215 and Panc286) and the spontaneous breast cancer model MMTV-PyMT were used. Animals were treated during 1 week of WoO treatment with vehicle or dovitinib, preceded and followed by [18F]-FMISO-PET, [18F]-FDG-PET, and histologic assessment (dextran extravasation, hypoxia and microvessel staining, and necrosis, cleaved caspase-3 and Ki67 measurements). After WoO treatment, gemcitabine (pancreas)/adriamycin (breast) or vehicle was added and animals were treated until the humane endpoint. Tumor growth inhibition (TGI) and survival were the parameters studied.
RESULTS
[18F]-FMISO SUV did not change after dovitinib-WoO treatment compared to vehicle-WoO (0.54 vs. 0.6) treatment in Panc215, but it decreased significantly in Panc286 (0.58 vs. 1.18; P < 0.05). In parallel, 10-KDa perivascular dextran extravasation was not reduced with dovitinib or vehicle-WoO treatment in Panc215, but it was reduced in Panc286. Whereas the addition of dovitinib to gemcitabine was indifferent in Panc215, it increased TGI in Panc286 (TGI switched from -59% to +49%). [18F]-FMISO SUV changes were accompanied by an almost 100% increase in interstitial gemcitabine delivery (665-1260 ng/mL). The results were validated in the PyMT model.
CONCLUSIONS
[18F]-FMISO accurately monitored vascular re-normalization and improved interstitial chemotherapy delivery.
Topics: Angiogenesis Inhibitors; Animals; Antimetabolites, Antineoplastic; Benzimidazoles; Breast; Breast Neoplasms; Cell Hypoxia; Cell Line, Tumor; Deoxycytidine; Female; Fluorine Radioisotopes; Humans; Mice; Mice, Nude; Misonidazole; Neovascularization, Pathologic; Pancreas; Pancreatic Neoplasms; Positron-Emission Tomography; Quinolones; Gemcitabine
PubMed: 26778791
DOI: 10.1016/j.molonc.2015.12.011 -
BMC Cancer Sep 2014Radiotherapy is an important treatment strategy for head and neck cancers. Tumor hypoxia and repopulation adversely affect the radiotherapy outcome. Accordingly,...
Dual tracer evaluation of dynamic changes in intratumoral hypoxic and proliferative states after radiotherapy of human head and neck cancer xenografts using radiolabeled FMISO and FLT.
BACKGROUND
Radiotherapy is an important treatment strategy for head and neck cancers. Tumor hypoxia and repopulation adversely affect the radiotherapy outcome. Accordingly, fractionated radiotherapy with dose escalation or altered fractionation schedule is used to prevent hypoxia and repopulation. 18F-fluoromisonidazole (FMISO) and 18F-fluorothymidine (FLT) are noninvasive markers for assessing tumor hypoxia and proliferation, respectively. Thus, we evaluated the dynamic changes in intratumoral hypoxic and proliferative states following radiotherapy using the dual tracers of 18F-FMISO and 3H-FLT, and further verified the results by immunohistochemical staining of pimonidazole (a hypoxia marker) and Ki-67 (a proliferation marker) in human head and neck cancer xenografts (FaDu).
METHODS
FaDu xenografts were established in nude mice and assigned to the non-radiation-treated control and two radiation-treated groups (10- and 20-Gy). Tumor volume was measured daily. Mice were sacrificed 6, 24, and 48 hrs and 7 days after radiotherapy. 18F-FMISO, and 3H-FLT and pimonidazole were injected intravenously 4 and 2 hrs before sacrifice, respectively. Intratumoral 18F-FMISO and 3H-FLT levels were assessed by autoradiography. Pimonidazole and Ki-67 immunohistochemistries were performed.
RESULTS
In radiation-treated mice, tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. Visual inspection showed that intratumoral 18F-FMISO and 3H-FLT distribution patterns were markedly different. Intratumoral 18F-FMISO level did not show significant changes after radiotherapy among the non-radiation-treated control and radiation-treated groups, whereas 3H-FLT level markedly decreased to 59 and 45% of the non-radiation-treated control at 6 hrs (p<0.0001) and then gradually increased with time in the 10- and 20-Gy-radiation-treated groups. The pimonidazole-positive hypoxic areas were visually similar in both the non-radiation-treated control and radiation-treated groups. No significant differences were observed in the percentage of pimonidazole-positive cells and Ki-67 index.
CONCLUSION
Intratumoral 18F-FMISO level did not change until 7 days, whereas 3H-FLT level markedly decreased at 6 hrs and then gradually increased with time after a single dose of radiotherapy. The concomitant monitoring of dynamic changes in tumor hypoxia and proliferation may provide important information for a better understanding of tumor biology after radiotherapy and for radiotherapy planning, including dose escalation and altered fractionation schedules.
Topics: Animals; Cell Proliferation; Disease Models, Animal; Head and Neck Neoplasms; Heterografts; Humans; Hypoxia; Male; Mice; Misonidazole; Radionuclide Imaging; Radiopharmaceuticals; Tumor Burden
PubMed: 25245041
DOI: 10.1186/1471-2407-14-692 -
Journal of Nuclear Medicine : Official... Mar 2016(18)F-fluoromisonidazole dynamic PET (dPET) is used to identify tumor hypoxia noninvasively. Its routine clinical implementation, however, has been hampered by the long...
UNLABELLED
(18)F-fluoromisonidazole dynamic PET (dPET) is used to identify tumor hypoxia noninvasively. Its routine clinical implementation, however, has been hampered by the long acquisition times required. We investigated the feasibility of kinetic modeling using shortened acquisition times in (18)F-fluoromisonidazole dPET, with the goal of expediting the clinical implementation of (18)F-fluoromisonidazole dPET protocols.
METHODS
Six patients with squamous cell carcinoma of the head and neck and 10 HT29 colorectal carcinoma-bearing nude rats were studied. In addition to an (18)F-FDG PET scan, each patient underwent a 45-min (18)F-fluoromisonidazole dPET scan, followed by 10-min acquisitions at 96 ± 4 and 163 ± 17 min after injection. Ninety-minute (18)F-fluoromisonidazole dPET scans were acquired in animals. Intratumor voxels were classified into 4 clusters based on their kinetic behavior using k-means clustering. Kinetic modeling was performed using the foregoing full datasets (FD) and repeated for each of 2 shortened datasets corresponding to the first approximately 100 min (SD1; patients only) or the first 45 min (SD2) of dPET data. The kinetic rate constants (KRCs) as calculated with a 2-compartment model for both SD1 and SD2 were compared with those derived from FD by correlation (Pearson), regression (Passing-Bablok), deviation (Bland-Altman), and classification (area-under-the-receiver-operating characteristic curve) analyses. Simulations were performed to assess uncertainties due to statistical noise.
RESULTS
Strong correlation (r ≥ 0.75, P < 0.001) existed between all KRCs deduced from both SD1 and SD2, and from FD. Significant differences between KRCs were found only for FD-SD2 correlations in patient studies. K1 and k3 were reproducible to within approximately 6% and approximately 30% (FD-SD1; patients) and approximately 4% and approximately 75% (FD-SD2; animals). Area-under-the-receiver-operating characteristic curve values for classification of patient clusters as hypoxic, using a tumor-to-blood ratio greater than 1.2, were 0.91 (SD1) and 0.86 (SD2). The percentage SD in estimating K1 and k3 from 45-min shortened datasets due to noise was less than 1% and between 2% and 12%, respectively.
CONCLUSION
Using single-session 45-min shortened (18)F-fluoromisonidazole dPET datasets appears to be adequate for the identification of intratumor regions of hypoxia. However, k3 was significantly overestimated in the clinical cohort. Further studies are necessary to evaluate the clinical significance of differences between the results as calculated from full and shortened datasets.
Topics: Algorithms; Animals; Carcinoma, Squamous Cell; Cohort Studies; Colorectal Neoplasms; HT29 Cells; Head and Neck Neoplasms; Humans; Hypoxia; Image Processing, Computer-Assisted; Misonidazole; Neoplasm Transplantation; Perfusion; ROC Curve; Radionuclide Imaging; Radiopharmaceuticals; Rats; Reproducibility of Results; Retrospective Studies
PubMed: 26609178
DOI: 10.2967/jnumed.115.160168