[11C]Methylation on a C18 Sep-Pak cartridge: a convenient way to produce [N-methyl-11C]choline

Pascali, C.; Bogni, A.; Iwata, Ren; Cambiè, Mara; Bombardieri, Emilio

doi:10.1002/(sici)1099-1344(200002)43:2<195::aid-jlcr316>3.0.co;2-p

Cited by 95 publications

(35 citation statements)

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“…The metabolic stability of 18 F-D4-FCH observed was not due to a high total cold compounds in the radiopharmaceutical, which may negatively impact on clearance. In contrast, the dose solution had higher specific activity (48.4 GBq/mmol) and pseudospecific activity (relative to the precursor D4-DMAE) than previously reported for 11 C-choline (34), the upper quality control release limit with respect to precursor being set at 10 mg (at least 10-to 20-fold lower). The lower levels of the precursor D4-DMAE along with the high specific activity are an added theoretic advantage, because DMAE is known to modulate the transport and phosphorylation of radiolabeled choline (35).…”

Section: Discussionmentioning

confidence: 96%

Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers

Challapalli

Sharma

Hallett³

et al. 2014

J Nucl Med

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11 C-choline and 18 F-fluoromethylcholine ( 18 F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radiotracer. A more metabolically stable FCH analog, 18 F-fluoromethyl-[1,2-2 H 4 ]choline ( 18 F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of 18 F-D4-FCH in 8 healthy human volunteers. Methods: 18 F-D4-FCH was intravenously administered as a bolus injection (mean 6 SD, 161 6 2.17 MBq; range, 156-163 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole-blood, plasma, and urine samples were collected for radioactivity measurement and plasma radiotracer metabolites. Tissue 18 F radioactivities were determined from quantitative analysis of the images, and time-activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time-activity curve normalized to injected activities and standard organ volumes. Dosimetry calculations were performed using OLINDA/EXM 1.1. Results: The injection of 18 F-D4-FCH was well tolerated in all subjects, with no radiotracer-related serious adverse event reported. The mean effective dose averaged over both men and women (6SD) was estimated to be 0.025 6 0.004 (men, 0.022 6 0.002; women, 0.027 6 0.002) mSv/MBq. The 5 organs receiving the highest absorbed dose (mGy/MBq) were the kidneys (0.106 6 0.03), liver (0.094 6 0.03), pancreas (0.066 6 0.01), urinary bladder wall (0.047 6 0.02), and adrenals (0.046 6 0.01). Elimination was through the renal and hepatic systems. Conclusion: 18 F-D4-FCH is a safe PET radiotracer with a dosimetry profile comparable to other common 18 F PET tracers. These data support the further development of 18 F-D4-FCH for clinical imaging of choline metabolism.

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Section: Discussionmentioning

confidence: 96%

Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers

Challapalli

Sharma

Hallett³

et al. 2014

J Nucl Med

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“…CHO was manufactured by standard methods at the local hospital as previously described (26,27). The mean injected activity of CHO measured 320 MBq (range 188-360 MBq) with mean specific radioactivity of 13,279 MBq/μmol and mean radiochemical purity of >99%.…”

Section: Methodsmentioning

confidence: 99%

[11C]Choline Positron Emission Tomography in Estrogen Receptor–Positive Breast Cancer

Contractor

Kenny

Stebbing

et al. 2009

Clinical Cancer Research

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Purpose: Novel radiotracers could potentially allow the identification of clinically aggressive tumor phenotypes. As choline metabolism increases during malignant transformation and progression of human mammary epithelial cells, we examined the ability of [11 C]choline (CHO) positron emission tomography imaging to detect clinically aggressive phenotype in patients with estrogen receptor (ER)-positive breast cancer in vivo. Experimental Design: CHO positron emission tomography was done in 32 individuals with primary or metastatic ER-positive breast cancer. Semiquantitative (standardized uptake value) and fully quantitative (net irreversible transfer rate constant of CHO, Ki) estimates of CHO uptake in the tumors were calculated and compared with tumor grade, size, involved nodes, and also ER, progesterone receptor, Ki-67, and human epidermal growth factor receptor-2 scores. Results: Breast tumors were well visualized in 30 of 32 patients with good tumor background ratios. A wide range of uptake values were observed in primary and metastatic tumors. CHO uptake variables correlated well with tumor grade. For most imaging variables, a poor association was found with tumor size, ER, progesterone receptor, human epidermal growth factor receptor-2, Ki-67, and nodal status. Conclusions: CHO showed good uptake in most breast cancers and merits further investigation as a breast cancer imaging agent. (Clin Cancer Res 2009;15(17):5503-10) Breast cancer is the commonest female malignancy with >1.2 million women diagnosed each year worldwide. Over 75% of breast carcinomas express estrogen receptor (ER). Hence, ERpositive breast cancer is usually treated with antiestrogens, such as tamoxifen. Adjuvant hormonal treatment with tamoxifen followed by an aromatase inhibitor for a total of 5 years (1), as well as aromatase inhibitors alone (2), have been shown to improve recurrence-free survival and overall survival. However, patients relapse despite adjuvant hormonal therapy, due to drug resistance. Only approximately half of the patients with recurrence in ER-positive disease respond to endocrine therapy, whereas the remainder show resistance, clinically evidenced by progression (3). The mechanisms underlying this process are complex, but it is generally agreed that, at least in some patients, cross-talk between cell surface receptor kinases and ER may play a role. In this regard, phosphorylation of ERα by the mitogen-activated protein kinase (MAPK; refs. 4-7) and phosphatidylinositol-3-kinase pathways (3) have been implicated. In particular, MAPK-mediated hyperphosphorylation of ERα on S118, S104, and S106 collectively leads to ligandindependent receptor activation, thereby potentially contributing to resistance to antiendocrine agents, such as tamoxifen and aromatase inhibitors (4,8,9). A large proportion of breast cancers have elevated MAPK (10), and expression correlates to poor response to endocrine therapies (11). There is an unmet need to develop imaging methods to guide clinicians as to the correct choice of su...

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“…11 C]choline [ 11 C]choline was synthesized according to the method of Pascali and colleagues (20) with minor modifications. [ 11 C]choline was produced with radiochemical yields of 80% to 90%, based on […”

Section: Synthesis Of [mentioning

confidence: 99%

The Sensitivity of [11C]Choline PET/CT to Localize Prostate Cancer Depends on the Tumor Configuration

Souvatzoglou

Weirich

Schwarzenboeck

et al. 2011

Clinical Cancer Research

100

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Purpose: To evaluate the dependency of the sensitivity of [11 C]choline positron emission tomography/ computed tomography (PET/CT) for detecting and localizing primary prostate cancer (PCa) on tumor configuration in the histologic specimen. Experimental Design: Forty-three patients with biopsy-proven PCa were included. They underwent radical prostatectomy within 31 days after [11 C]choline PET/CT. The transaxial image slices and the histologic specimens were analyzed by comparing the respective slices. Maximum standardized uptake values (SUV max ) were calculated in each segment and correlated with histopathology. The tumor configuration in the histologic specimen was grouped as: I, unifocal; II, multifocal; III, rind-like shaped; IV, size <5 mm. Data analysis included the investigation of detection of PCa by SUV max , the assessment of the influence of potential contributing factors on tumor prediction, and the evaluation of whether SUV could discriminate cancer tissue from benign prostate hyperplasia (BPH), prostatitis, HGPIN (high-grade prostate intraepithelial neoplasm), or normal prostate tissue. General estimation equation models were used for statistical analysis.Results: Tumor configuration in histology was classified as I in 21 patients, as II in 9, as III in 5, and as IV in 8. The prostate segment involved by cancer is identified in 79% of the patients. SUV max was located in the same side of the prostate in 95% of patients. Tumor configuration was the only factor significantly negatively influencing tumor prediction (P < 0.001). PCa-SUV max (median SUV max ¼ 4.9) was not significantly different from BPH-SUV (median SUV max ¼ 4.5) and prostatitis-SUV (median SUV max ¼ 3.9), P ¼ 0.102 and P ¼ 0.054, respectively.Conclusions: The detection and localization of PCa in the prostate with [ 11 C]choline PET/CT is impaired by tumor configuration. Additionally, in our patient population, PCa tissue could not be distinguished from benign pathologies in the prostate.

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[11C]Methylation on a C18 Sep-Pak cartridge: a convenient way to produce [N-methyl-11C]choline

Cited by 95 publications

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Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers

Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers

[11C]Choline Positron Emission Tomography in Estrogen Receptor–Positive Breast Cancer

The Sensitivity of [11C]Choline PET/CT to Localize Prostate Cancer Depends on the Tumor Configuration

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[11C]Methylation on a C18 Sep-Pak cartridge: a convenient way to produce [N-methyl-11C]choline

Cited by 95 publications

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Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

[11C]Choline Positron Emission Tomography in Estrogen Receptor–Positive Breast Cancer

The Sensitivity of [11C]Choline PET/CT to Localize Prostate Cancer Depends on the Tumor Configuration

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Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers

Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers