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The clinical safety, biodistribution and internal radiation dosimetry of flutemetamol (¹⁸F) injection in healthy Japanese adult volunteers.

Senda M, Brooks DJ, Farrar G, Somer EJ, Paterson CL, Sasaki M, McParland BJ - Ann Nucl Med (2015)

Bottom Line: Flutemetamol ((18)F) injection was well tolerated.The mean effective dose was 34.9 μSv/MBq.The clinical safety of [(18)F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Imaging, Institute of Biomedical Research and Innovation, Kobe, Japan.

ABSTRACT

Objectives: The Phase I safety, biodistribution and internal radiation dosimetry study in adult healthy Japanese males of flutemetamol ((18)F) injection, an in vivo β-amyloid imaging agent, is reported and compared with previously obtained Caucasian data.

Methods: Whole-body PET scans of 6 healthy volunteers (age 51.8-61.7 years) were acquired approximately 4 h post-injection (administered activity 102-160 MBq). Venous blood sampling determined (18)F activity concentrations in whole blood and plasma and high-performance liquid chromatography (HPLC) established the percentages of parent [(18)F]flutemetamol and its metabolites. Voided urine activity was recorded. The decay-corrected and normalised (18)F activity of 14 source organ regions as a function of time was entered into the OLINDA/EXM software to calculate the internal radiation dosimetry and effective dose of each subject following the MIRD schema. The pharmacokinetics, biodistribution and dosimetry profiles were compared to data obtained from a cohort of healthy Caucasian adult volunteers from a previous Phase I study of [(18)F]flutemetamol.

Results: Flutemetamol ((18)F) injection was well tolerated. The highest mean initial uptakes were measured in the liver (15.2%), lungs (10.2%) and brain (6.6%). The highest mean radiation absorbed doses were received by the gallbladder wall (366 μGy/MBq), upper large intestine (138 μGy/MBq) and small intestine (121 μGy/MBq). The mean effective dose was 34.9 μSv/MBq. HPLC analysis demonstrated that at 5-min post-injection about 75% of plasma (18)F radioactivity was in the form of parent [(18)F]flutemetamol, reducing to 8 and 2% at 25 and 90 min, respectively, giving rise to less lipophilic (18)F-labelled metabolites. Comparisons with the Caucasian cohort showed no differences that could be regarded as clinically significant.

Conclusion: The clinical safety of [(18)F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults.

No MeSH data available.


Related in: MedlinePlus

HPLC radiochromatograms for a plasma sample spiked ex vivo with standard [18F]flutemetamol, and for the plasma obtained from a representative subject at b 5, c 30 and d 90 min after administration of flutemetamol (18F) injection. The vertical axis shows “Radioactivity detector response (mV)” while the “Retention time (min)” appears on the horizontal axis. Region 3 corresponds to the [18F]flutemetamol parent in b, c and d as identified in a. Regions 1 and 2 correspond to metabolites that are more hydrophilic than the parent of Region 3, and Region 4 represents a minor lipophilic metabolite
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Fig4: HPLC radiochromatograms for a plasma sample spiked ex vivo with standard [18F]flutemetamol, and for the plasma obtained from a representative subject at b 5, c 30 and d 90 min after administration of flutemetamol (18F) injection. The vertical axis shows “Radioactivity detector response (mV)” while the “Retention time (min)” appears on the horizontal axis. Region 3 corresponds to the [18F]flutemetamol parent in b, c and d as identified in a. Regions 1 and 2 correspond to metabolites that are more hydrophilic than the parent of Region 3, and Region 4 represents a minor lipophilic metabolite

Mentions: Figure 3 presents the mean washout of activity from whole blood and plasma. The plasma activity data from the previous study on Caucasians (ALZ103) [6] are also shown for comparison in Fig. 3. Figure 4 shows the HPLC traces of 18F activity in plasma from a representative subject. The signals of hydrophilic species exhibit a decreased retention time. Figure 4a shows the radiochromatogram for a human plasma sample spiked ex vivo with the parent [18F]flutemetamol and Fig. 4b–d shows radiochromatograms obtained at 5, 25 and 90 min pi, respectively. When the total radioactivity recovered in the HPLC effluent was compared with the activity in each plasma sample applied to the HPLC, the recovery rate (effluent/plasma) was 0.98 ± 0.16, indicating that all the activity in the plasma samples was accounted for in the radio-HPLC analysis.Fig. 3


The clinical safety, biodistribution and internal radiation dosimetry of flutemetamol (¹⁸F) injection in healthy Japanese adult volunteers.

Senda M, Brooks DJ, Farrar G, Somer EJ, Paterson CL, Sasaki M, McParland BJ - Ann Nucl Med (2015)

HPLC radiochromatograms for a plasma sample spiked ex vivo with standard [18F]flutemetamol, and for the plasma obtained from a representative subject at b 5, c 30 and d 90 min after administration of flutemetamol (18F) injection. The vertical axis shows “Radioactivity detector response (mV)” while the “Retention time (min)” appears on the horizontal axis. Region 3 corresponds to the [18F]flutemetamol parent in b, c and d as identified in a. Regions 1 and 2 correspond to metabolites that are more hydrophilic than the parent of Region 3, and Region 4 represents a minor lipophilic metabolite
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4526582&req=5

Fig4: HPLC radiochromatograms for a plasma sample spiked ex vivo with standard [18F]flutemetamol, and for the plasma obtained from a representative subject at b 5, c 30 and d 90 min after administration of flutemetamol (18F) injection. The vertical axis shows “Radioactivity detector response (mV)” while the “Retention time (min)” appears on the horizontal axis. Region 3 corresponds to the [18F]flutemetamol parent in b, c and d as identified in a. Regions 1 and 2 correspond to metabolites that are more hydrophilic than the parent of Region 3, and Region 4 represents a minor lipophilic metabolite
Mentions: Figure 3 presents the mean washout of activity from whole blood and plasma. The plasma activity data from the previous study on Caucasians (ALZ103) [6] are also shown for comparison in Fig. 3. Figure 4 shows the HPLC traces of 18F activity in plasma from a representative subject. The signals of hydrophilic species exhibit a decreased retention time. Figure 4a shows the radiochromatogram for a human plasma sample spiked ex vivo with the parent [18F]flutemetamol and Fig. 4b–d shows radiochromatograms obtained at 5, 25 and 90 min pi, respectively. When the total radioactivity recovered in the HPLC effluent was compared with the activity in each plasma sample applied to the HPLC, the recovery rate (effluent/plasma) was 0.98 ± 0.16, indicating that all the activity in the plasma samples was accounted for in the radio-HPLC analysis.Fig. 3

Bottom Line: Flutemetamol ((18)F) injection was well tolerated.The mean effective dose was 34.9 μSv/MBq.The clinical safety of [(18)F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Imaging, Institute of Biomedical Research and Innovation, Kobe, Japan.

ABSTRACT

Objectives: The Phase I safety, biodistribution and internal radiation dosimetry study in adult healthy Japanese males of flutemetamol ((18)F) injection, an in vivo β-amyloid imaging agent, is reported and compared with previously obtained Caucasian data.

Methods: Whole-body PET scans of 6 healthy volunteers (age 51.8-61.7 years) were acquired approximately 4 h post-injection (administered activity 102-160 MBq). Venous blood sampling determined (18)F activity concentrations in whole blood and plasma and high-performance liquid chromatography (HPLC) established the percentages of parent [(18)F]flutemetamol and its metabolites. Voided urine activity was recorded. The decay-corrected and normalised (18)F activity of 14 source organ regions as a function of time was entered into the OLINDA/EXM software to calculate the internal radiation dosimetry and effective dose of each subject following the MIRD schema. The pharmacokinetics, biodistribution and dosimetry profiles were compared to data obtained from a cohort of healthy Caucasian adult volunteers from a previous Phase I study of [(18)F]flutemetamol.

Results: Flutemetamol ((18)F) injection was well tolerated. The highest mean initial uptakes were measured in the liver (15.2%), lungs (10.2%) and brain (6.6%). The highest mean radiation absorbed doses were received by the gallbladder wall (366 μGy/MBq), upper large intestine (138 μGy/MBq) and small intestine (121 μGy/MBq). The mean effective dose was 34.9 μSv/MBq. HPLC analysis demonstrated that at 5-min post-injection about 75% of plasma (18)F radioactivity was in the form of parent [(18)F]flutemetamol, reducing to 8 and 2% at 25 and 90 min, respectively, giving rise to less lipophilic (18)F-labelled metabolites. Comparisons with the Caucasian cohort showed no differences that could be regarded as clinically significant.

Conclusion: The clinical safety of [(18)F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults.

No MeSH data available.


Related in: MedlinePlus