Dataset Information

Kinetic Evaluation of the Hypoxia Radiotracers [¹⁸F]FMISO and [¹⁸F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

ABSTRACT:

Purpose

We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors.

Methods

Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMR_max) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. TMR_max was compared with radiotracer trapping rate (k ₃), influx rate (K _i), and distribution volume (V _T).

Results

Tumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. TMR_max was strongly correlated with the irreversible parameters (k ₃ and K _i) for [18F]FMISO at > 90 min and with the reversible parameter (V _T) for [18F]FAZA at > 120 min.

Conclusions

Our results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation between TMR_max over the 90-150 min and 120-150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement (TMR_max) is a good alternative to quantify tumor hypoxia.

Supplementary information

The online version contains supplementary material available at 10.1007/s13139-022-00780-4.

SUBMITTER: Choen S

PROVIDER: S-EPMC9832187 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Kinetic Evaluation of the Hypoxia Radiotracers [<sup>18</sup>F]FMISO and [<sup>18</sup>F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Choen Sangkyung S Kent Michael S MS Chaudhari Abhijit J AJ Cherry Simon R SR Krtolica Ana A Zwingenberger Allison L AL

Nuclear medicine and molecular imaging 20221011 1

<h4>Purpose</h4>We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors.<h4>Methods</h4>Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMR<sub>max</sub>) > 1.4 on th ...[more]

PMID: 36643946

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Project description:BackgroundEsophageal cancer is an aggressive disease with poor survival rates. A more patient-tailored approach based on predictive biomarkers could improve outcome. We aimed to predict radiotherapy (RT) response by imaging tumor hypoxia with 18F-FAZA PET/CT in an esophageal adenocarcinoma (EAC) mouse model. Additionally, we investigated the radiosensitizing effect of the hypoxia modifier nimorazole in vitro and in vivo.MethodsIn vitro MTS cell proliferation assays (OACM5 1.C SC1, human EAC cell line) were performed under normoxic and hypoxic (< 1%) conditions: control (100 μL PBS), nimorazole, irradiation (5, 10 or 20 Gy) with or without nimorazole. In vivo, subcutaneous xenografts were induced in nude mice (OACM5 1.C SC1). Treatment was given daily for 5 consecutive days: (A) control (600 μl NaCl 0.9% intraperitoneally (IP)) (N = 5, n = 7), (B) RT (5 Gy/d) (N = 11, n = 20), (C) combination (nimorazole (200 mg/kg/d IP) 30 min before RT) (N = 13, n = 21). N = number of mice, n = number of tumors. 18F-FAZA PET/CT was performed before treatment and tumor to background (T/B) ratios were calculated. Relative tumor growth was calculated and tumor sections were examined histologically (hypoxia, proliferation).ResultsA T/B ≥ 3.59 on pre-treatment 18F-FAZA PET/CT was predictive for worse RT response (sensitivity 92.3%, specificity 71.4%). Radiation was less effective in hypoxic tumors (T/B ≥ 3.59) compared to normoxic tumors (T/B < 3.59) (P = 0.0025). In vitro, pre-treatment with nimorazole significantly decreased hypoxic radioresistance (P < 0.01) while in vivo, nimorazole enhanced the efficacy of RT to suppress cancer cell proliferation in hypoxic tumor areas (Ki67, P = 0.064), but did not affect macroscopic tumor growth.ConclusionsTumor tissue hypoxia as measured with 18F-FAZA PET/CT is predictive for RT response in an EAC xenograft model. The radiosensitizing effect of nimorazole was questionable and requires further investigation.

Project description:BackgroundWhile [18F]fluoromisonidazole (FMISO), a representative PET tracer to detect hypoxia, is reported to be able to prospect the prognosis after treatment for various types of cancers, the relation is unclear for pancreatic cancer. The aim of this study is to assess the feasibility of [18F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer.MethodsPatients with pancreatic cancer who had been initially planned for surgery received [18F]FMISO PET/CT. Peak standardized uptake value (SUV) of the pancreatic tumor was divided by SUVpeak of the aorta, and tumor blood ratio using SUVpeak (TBRpeak) was calculated. After preoperative examination, surgeons finally decided the operability of the patients. TBRpeak was compared with hypoxia-inducible factor (HIF)-1α immunohistochemistry when the tissues were available. Furthermore, correlation of TBRpeak with the recurrence-free survival and the overall survival were evaluated by Kaplan-Meyer methods.ResultsWe analyzed 25 patients with pancreatic adenocarcinoma (11 women and 14 men, median age, 73 years; range, 58-81 years), and observed for 39-1101 days (median, 369 days). Nine cases (36.0%) were identified as visually positive of pancreatic cancer on [18F]FMISO PET/CT images. TBRpeak of the negative cases was significantly lower than that of the positive cases (median 1.08, interquartile range (IQR) 1.02-1.15 vs median 1.50, IQR 1.25-1.73, p < 0.001), and the cutoff TBRpeak was calculated as 1.24. Five patients were finally considered inoperable. There was no significant difference in TBRpeak of inoperable and operable patients (median 1.48, IQR 1.06-1.98 vs median 1.12, IQR 1.05-1.21, p = 0.10). There was no significant difference between TBRpeak and HIF-1α expression (p = 0.22). The patients were dichotomized by the TBRpeak cutoff, and the higher group showed significantly shorter recurrence-free survival than the other (median 218 vs 441 days, p = 0.002). As for overall survival of 20 cases of operated patients, the higher TBRpeak group showed significantly shorter overall survival than the other (median survival, 415 vs > 1000 days, p = 0.04).Conclusions[18F]FMISO PET/CT has the possibility to be a preoperative prognostic factor in patients with pancreatic cancer.

Project description:BackgroundTo facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[18F]-fluoropropyl)-2-nitroimidazole ([18F]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [18F]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [18F]fluoromisonidazole ([18F]FMISO).ResultsThe single administration of [18F]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings. Dynamic and sequential whole-body scans showed that [18F]DiFA was rapidly cleared from all of the organs via the hepatobiliary and urinary systems. The whole-body mean effective dose of [18F]DiFA estimated by using the medical internal radiation dose (MIRD) schema with organ level internal dose assessment/exponential modeling (OLINDA/EXM) computer software 1.1 was 14.4 ± 0.7 μSv/MBq. Among the organs, the urinary bladder received the largest absorbed dose (94.7 ± 13.6 μSv/MBq). The mean absorbed doses of the other organs were equal to or less than those from other hypoxia tracers. The excretion of radioactivity via the urinary system was very rapid, reaching 86.4 ± 7.1% of the administered dose. For the preliminary clinical study, seven patients were subjected to [18F]FMISO and [18F]DiFA positron emission tomography (PET) at 48-h intervals to compare the two tracers' diagnostic ability for tumor hypoxia. The results of the tumor hypoxia evaluation by [18F]DiFA PET at 1 h and 2 h were not significantly different from those obtained with [18F]FMISO PET at 4 h ([18F]DiFA at 1 h, p = 0.32; [18F]DiFA at 2 h, p = 0.08). Moreover, [18F]DiFA PET at both 1 h (k = 0.68) and 2 h (k = 1.00) showed better inter-observer reproducibility than [18F]FMISO PET at 4 h (k = 0.59).Conclusion[18F]DiFA is well tolerated, and its radiation dose is comparable to those of other hypoxia tracers. [18F]DiFA is very rapidly cleared via the urinary system. [18F]DiFA PET generated comparable images to [18F]FMISO PET in hypoxia imaging with shorter waiting time, demonstrating the promising potential of [18F]DiFA PET for hypoxia imaging and for a multicenter trial.

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Dataset Information

Kinetic Evaluation of the Hypoxia Radiotracers [¹⁸F]FMISO and [¹⁸F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Purpose

Methods

Results

Conclusions

Supplementary information

Publications

Kinetic Evaluation of the Hypoxia Radiotracers [<sup>18</sup>F]FMISO and [<sup>18</sup>F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Kinetic Evaluation of the Hypoxia Radiotracers [18F]FMISO and [18F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Purpose

Methods

Results

Conclusions

Supplementary information

Publications

Kinetic Evaluation of the Hypoxia Radiotracers [<sup>18</sup>F]FMISO and [<sup>18</sup>F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Kinetic Evaluation of the Hypoxia Radiotracers [¹⁸F]FMISO and [¹⁸F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.