Selection Criteria for Determination of Optimal Reconstruction Method for Cu-64 Trastuzumab Dosimetry on Siemens Inveon PET Scanner

Lee, Seonhwa; Kim, Il Tae; Kang, Ye-rin; Kim, Hyungwoo; Kim, Jung Young; Lee, Yongjin; Kim, Jung Min; Kim, Jin Su

doi:10.3390/jcm8040512

Cited by 4 publications

(6 citation statements)

References 22 publications

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“…Consequently, this mathematical relationship and simplified underestimation correction factor can be conveniently used to optimise future dosimetry estimates of novel PET radiotracers in a systematic manner. It is also encouraging to observe that the underestimation bias measured with 18 F-labelled radiotracers was also previously reported by others using a radiotracer labelled with copper-64 16 . This suggests the mathematical relationships observed in this dosimetry study may persist in a broader nuclear medicine context and likely for different radioisotopes, including for example alpha and beta emitters used in radiation therapy studies, thus, representing a systematic error in PET dosimetry calculations based on preclinical models.…”

Section: Discussionsupporting

confidence: 83%

“…Although the impact of reconstruction methods on radionuclide dose estimates has been sparsely investigated in previous clinical 14,15 and preclinical 16 studies, there is little understanding of the mathematical relationships of this bias and whether it is due to systematic errors or random and radiotracer-dependent differences. The results of the six radiotracers used in this study show a significant and strong linear relationship between predicted clinical dosimetry from preclinical models versus clinical models when using FBP and rat:human normalised data.…”

Section: Discussionmentioning

confidence: 99%

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Preclinical dosimetry models and the prediction of clinical doses of novel positron emission tomography radiotracers

Garrow

Andrews

Gonzalez

et al. 2020

Sci Rep

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Dosimetry models using preclinical positron emission tomography (PET) data are commonly employed to predict the clinical radiological safety of novel radiotracers. However, unbiased clinical safety profiling remains difficult during the translational exercise from preclinical research to first-in-human studies for novel PET radiotracers. In this study, we assessed PET dosimetry data of six 18F-labelled radiotracers using preclinical dosimetry models, different reconstruction methods and quantified the biases of these predictions relative to measured clinical doses to ease translation of new PET radiotracers to first-in-human studies. Whole-body PET images were taken from rats over 240 min after intravenous radiotracer bolus injection. Four existing and two novel PET radiotracers were investigated: [18F]FDG, [18F]AlF-NOTA-RGDfK, [18F]AlF-NOTA-octreotide ([18F]AlF-NOTA-OC), [18F]AlF-NOTA-NOC, [18F]ENC2015 and [18F]ENC2018. Filtered-back projection (FBP) and iterative methods were used for reconstruction of PET data. Predicted and true clinical absorbed doses for [18F]FDG and [18F]AlF-NOTA-OC were then used to quantify bias of preclinical model predictions versus clinical measurements. Our results show that most dosimetry models were biased in their predicted clinical dosimetry compared to empirical values. Therefore, normalization of rat:human organ sizes and correction for reconstruction method biases are required to achieve higher precision of dosimetry estimates.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Preclinical dosimetry models and the prediction of clinical doses of novel positron emission tomography radiotracers

Garrow

Andrews

Gonzalez

et al. 2020

Sci Rep

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“…Subcutaneous tumors were formed after subcutaneous injection of MKN1-Luc, KATO III, and MKN45-Luc cells. Previous reports have shown that N87, NUGC4 and OCUM-1 can form subcutaneous tumors in nude mice (14)(15)(16)(17)(18).…”

Section: Resultsmentioning

confidence: 99%

Establishment of Peritoneal and Hepatic Metastasis Mouse Xenograft Models Using Gastric Cancer Cell Lines

Miwa

Kanda

Umeda

et al. 2019

In Vivo

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Background/Aim: Establishment of mouse xenograft models is necessary for oncological research and depends on the characteristics of the cell lines and the immune system of the host. In this study, we describe the development of mouse xenograft models using human gastric cancer (GC) cell lines. Materials and Methods: MKN1 stably-expressing luciferase (MKN1-Luc), N87, KATO III, MKN45 stably-expressing luciferase (MKN45-Luc), NUGC4, and OCUM-1 human GC cell lines were injected intraperitoneally into mice to establish peritoneal metastasis models. MKN45-Luc were injected into subcutaneously implanted spleen, and MKN1-Luc and MKN45-Luc were injected directly into the portal veins of mice for the establishment of hepatic metastasis models. Results: Peritoneal metastasis was formed after implantation of MKN1-Luc, N87, KATO III, MKN45-Luc, and NUGC4 in nude mice, but not formed in OCUM-1 even in NOD/SCID mice. After intrasplenic injection of MKN45-Luc, we found no hepatic metastasis formation. We identified hepatic metastasis formation after direct injection of MKN45-Luc and MKN1-Luc into the portal veins of NOD/SCID mice. Conclusion: Peritoneal and hepatic metastasis mouse xenograft models were successfully established using several human GC cell lines. Gastric cancer (GC) is the fourth leading cause of cancerrelated death worldwide (1). Perioperative adjuvant therapy has improved prognosis to a certain degree (2-4). However, Materials and Methods Cell lines and cell culture. MKN1 cells stably expressing luciferase (MKN1-Luc), MKN45 cells stably expressing luciferase (MKN45-Luc), NUGC4, and OCUM-1 were obtained from the Japanese Collection of Research Bio Resources Cell Bank (JCRB) (Osaka, Japan). N87 and KATO III cell lines were purchased from the American Type Culture Collection (ATCC; Manassas, VA, USA). Cells were incubated at 37˚C with 5% CO 2 in the recommended medium supplemented with 10% fetal bovine serum. The characteristics of the gastric cancer cell lines are listed in Table I.

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“…Cu-64-TRZ could be used for both diagnosis and therapy. Previously, an antigen-responsive molecular sensor study with TRZ [24], a comparison study of chelator [25], dosimetry studies of Cu-64-TRZ PET [13,26], and a study of I-131 TRZ using a HER2+ NCI N87 xenograft mouse model [27] were conducted. However, tumor microenvironments such as angiogenesis, fibrosis, and proliferation were not considered in those previous studies [13,24,25,26,27].…”

Section: Discussionmentioning

confidence: 99%

“…High accumulation of radionuclides at the tumor periphery would be more harmful to normal healthy tissues, especially in the case of long-range beta-emitting radioisotopes like Cu-64, Y-90, and I-131. Cu-64, with positron energy of 0.656 MeV and position range of 0.70 mm, also emits β – and Auger electrons and has potential for radiotherapy [13]. Since uniform distribution and deeper penetration of mAbs in tumor tissue are attractive goals in developing RIT for solid tumors, two dosage regimens of Cu-64-trastuzumab (TRZ) with paclitaxel as SD (300 μg TRZ on D0, 70 mg/kg paclitaxel on D1) and FD (150 μg TRZ on D0 or D3, 40 and 30 mg/kg paclitaxel on D1 or D4) could suggest dosage rationalization in terms of their therapeutic efficacy based on our previous results [14].…”

Section: Introductionmentioning

confidence: 99%

Comparison between Fractionated Dose and Single Dose of Cu-64 Trastuzumab Therapy in the NCI-N87 Gastric Cancer Mouse Model

Zaheer

Kim

Lee

et al. 2019

IJMS

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For optimum radioimmunotherapy (RIT), deep penetration and uniform distribution into the tumor core is important. The solid tumor microenvironment, consisting of a highly fibrotic or desmoplastic tumor, abnormal tumor vasculature, high fluid pressure, and the absence of fluid lymphatics, limits the distribution of monoclonal antibodies mAbs to the tumor core. To investigate the optimal rationale for therapeutic mAbs administration and the microdistribution of mAbs, single and serial fractional dosage regimens of Cu-64-trastuzumab (TRZ) with paclitaxel were evaluated. Groups of nude mice were inoculated with gastric cancer cell line NCI-N87 tumor cells. When the tumor size reached 200 ± 20 mm3, the mice were divided into two groups for injection of Alexa-647-TRZ. One group (n = 5) was injected with 15 mg/kg in a single dose (SD), and the other group (n = 5) with two doses of 7.5 mg/kg (fractionated dose (FD)). In both cases, the injections were done intravenously in combination with intraperitoneal paclitaxel either as a SD of 70 mg/kg or fractionated into two doses of 40 and 30 mg/kg. Tumors were harvested, flash frozen, and sectioned (8 µm) five days after Alexa-647-TRZ injection. Rhodamine lectin (rhodamine-labeled Ricinus communis agglutinin I, 1 mg in 0.2 mL of phosphate-buffered saline (PBS)) was intravenously injected to delineate the functional vessel for a wait time of 5 min before animal euthanization. Microscopic images were acquired with an IN Cell Analyzer. The amount of TRZ that penetrated the tumor surface and the tumor vessel was calculated by area under the curve (AUC) analysis. For RIT efficacy (n = 21), Cu-64-TRZ was injected following the same dose schedule to observe tumor volume and survival ratio for 30 days. The SD and FD regimens of Alexa-647-TRZ were observed to have no significant difference in penetration of mAbs from the tumor edge and vessel, nor was the total accumulation across the whole tumor tissue significantly different. Additionally, the SD and FD regimens of Cu-64-TRZ were not proven to be significantly efficacious. Our study reveals that SD and FD in a treatment design with Cu-64-TRZ and paclitaxel shows no significant difference in therapeutic efficacy on tumor growth inhibition in vivo in mice bearing human gastric cancer xenografts overexpressing HER2 antigen.

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Selection Criteria for Determination of Optimal Reconstruction Method for Cu-64 Trastuzumab Dosimetry on Siemens Inveon PET Scanner

Cited by 4 publications

References 22 publications

Preclinical dosimetry models and the prediction of clinical doses of novel positron emission tomography radiotracers

Preclinical dosimetry models and the prediction of clinical doses of novel positron emission tomography radiotracers

Establishment of Peritoneal and Hepatic Metastasis Mouse Xenograft Models Using Gastric Cancer Cell Lines

Comparison between Fractionated Dose and Single Dose of Cu-64 Trastuzumab Therapy in the NCI-N87 Gastric Cancer Mouse Model

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