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European Journal of Nuclear Medicine... Aug 2023To introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine I therapy (RAI) for...
The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients.
PURPOSE
To introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine I therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by I PET.
METHODS
Patients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUV > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-I to determine the individual lesion radiation-absorbed dose. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion radiation dose metrics, with candidate biomarkers ("predictors") such as SUV and activity in microcurie per gram, from a single imaging timepoint.
RESULTS
In the 169 lesions (in 15 patients) that received I therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming wide heterogeneity of lesion radiation dose. Initial findings from the prediction curve on all 208 lesions confirmed that a 48-h SUV was the best predictor of lesion radiation dose and permitted calculation of the I activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals.
CONCLUSIONS
Based on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint I-PET-based dosimetry biomarker for RAI in patients with mDTC. The approach provides clinicians with a tool to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed dose (cGy) for selected index lesions based on a single 48-h measurement I-PET image, provided the selected activity does not exceed the maximum tolerated activity (MTA) of < 2 Gy to blood, as is standard of care at Memorial Sloan Kettering Cancer Center.
TRIAL REGISTRATION
NCT04462471, Registered July 8, 2020. NCT03647358, Registered Aug 27, 2018.
Topics: Humans; Adenocarcinoma; Iodine Radioisotopes; Radiation Dosage; Thyroid Neoplasms
PubMed: 37171634
DOI: 10.1007/s00259-023-06240-1 -
Frontiers in Bioengineering and... 2019To investigate the therapeutic efficacy of intratumoral injection of I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by...
To investigate the therapeutic efficacy of intratumoral injection of I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by Tc-HYNIC-duramycin and Tc-HYNIC-3PRGD2 SPECT/CT imaging. HCC xenograft tumor mice models were injected intratumorally with a single dose of normal saline, 10 microcurie (μCi) I-AA98 mAb, free I, AA98 mAb, 80 μCi I-AA98 mAb, and 200 μCi I-AA98 mAb. Tc-HYNIC-duramycin and Tc-HYNIC-3PRGD2 micro-SPECT/CT imaging were performed on days 3 and 7, respectively. The T/M ratio for each imaging was compared with the corresponding immunohistochemical staining at each time point. The relative tumor inhibition rates were documented. In terms of apoptosis, the 200 μCi group demonstrated the highest apoptotic index (11.8 ± 3.8%), and its T/M ratio achieved by Tc-HYNIC-duramycin imaging on day 3 was higher than that of the normal saline group, 80 μCi group, 10 μCi group and free I group on day 3, respectively (all < 0.05). On day 3, there was a markedly positive correlation between T/M ratio from Tc-HYNIC-duramycin imaging and apoptotic index by TUNEL staining ( = 0.6981; < 0.05). Moreover, the 200 μCi group showed the lowest T/M ratio on Tc-HYNIC-3PRGD2 imaging (1.0 ± 0.5) on day 7 (all < 0.05) comparing to other groups. The T/M ratio on day 7 was not correlated with integrin αβ staining ( > 0.05). The relative inhibitory rates of tumor on day 14 in the AA98 mAb, 10 μCi, 80 μCi, free I, and 200 μCi groups were 26.3, 55.3, 60.5, 66.3, and 69.5%, respectively. I-AA98 mAb showed more effective apoptosis induced ability for CD146 high expression Hep G2 HCC cells and hold the potential for HCC treatment. Moreover, Tc-HYNIC-Duramycin (apoptosis-targeted) imaging and Tc-HYNIC-3PRGD2 (angiogenesis-targeted) imaging are reliable non-invasive methods to evaluate the efficacy of targeted treatment of HCC.
PubMed: 31799244
DOI: 10.3389/fbioe.2019.00319