TY - JOUR
T1 - 18F-ML-10, a PET tracer for apoptosis
T2 - First human study
AU - Höglund, Johanna
AU - Shirvan, Anat
AU - Antoni, Gunnar
AU - Gustavsson, Sven Åke
AU - Långström, Bengt
AU - Ringheim, Anna
AU - Sörensen, Jens
AU - Ben-Ami, Miri
AU - Ziv, Ilan
PY - 2011/5/1
Y1 - 2011/5/1
N2 - Clinical PET of apoptosis may have substantial value in advancing patient care. We report here the first-in-humans study with 18F-labeled 2-(5-fluoropentyl)-2-methyl malonic acid (18F-ML-10), a small-molecule PET tracer for apoptosis. Presented are the dosimetry, biodistribution, stability, and safety profiles of this PET tracer in healthy human volunteers. Also reported is tracer binding to targeted apoptotic cells in testicular tissue, where a relative abundance of apoptotic cells is normally observed. Methods: 18F-ML-10 (233 ± 90 MBq) was intravenously administered to 8 healthy subjects, followed by whole-body PET/CT for 220 min. Serial blood and urine samples were collected for radioactivity measurement, and plasma tracer stability was assessed by high-performance liquid chromatography. Dosimetry calculations were performed using OLINDA/EXM software. Results: 18F-ML-10 manifested high stability in vivo and rapid distribution followed by fast clearance, with an elimination half-life of 1.3 ± 0.1 and 1.1 ± 0.2 h from the blood and from all other organs, respectively, and excretion through the urine. Dosimetry showed an average effective whole-body dose of 15.4 ± 3.7 μSv/MBq, with the urinary bladder being the dose-limiting organ. Selective accumulation and retention of the tracer in the testes was observed in all male subjects, a finding also demonstrated in mice using both small-animal PET and histopathology, confirming binding to apoptotic cells. Administration of 18F-ML-10 was safe, without adverse effects. Conclusion: 18F-ML-10 administered to healthy humans demonstrated a favorable dosimetry, biodistribution, stability, and safety profile. Binding to apoptotic sites was also demonstrated. These data support further development of this small-molecule probe for clinical PET of apoptosis.
AB - Clinical PET of apoptosis may have substantial value in advancing patient care. We report here the first-in-humans study with 18F-labeled 2-(5-fluoropentyl)-2-methyl malonic acid (18F-ML-10), a small-molecule PET tracer for apoptosis. Presented are the dosimetry, biodistribution, stability, and safety profiles of this PET tracer in healthy human volunteers. Also reported is tracer binding to targeted apoptotic cells in testicular tissue, where a relative abundance of apoptotic cells is normally observed. Methods: 18F-ML-10 (233 ± 90 MBq) was intravenously administered to 8 healthy subjects, followed by whole-body PET/CT for 220 min. Serial blood and urine samples were collected for radioactivity measurement, and plasma tracer stability was assessed by high-performance liquid chromatography. Dosimetry calculations were performed using OLINDA/EXM software. Results: 18F-ML-10 manifested high stability in vivo and rapid distribution followed by fast clearance, with an elimination half-life of 1.3 ± 0.1 and 1.1 ± 0.2 h from the blood and from all other organs, respectively, and excretion through the urine. Dosimetry showed an average effective whole-body dose of 15.4 ± 3.7 μSv/MBq, with the urinary bladder being the dose-limiting organ. Selective accumulation and retention of the tracer in the testes was observed in all male subjects, a finding also demonstrated in mice using both small-animal PET and histopathology, confirming binding to apoptotic cells. Administration of 18F-ML-10 was safe, without adverse effects. Conclusion: 18F-ML-10 administered to healthy humans demonstrated a favorable dosimetry, biodistribution, stability, and safety profile. Binding to apoptotic sites was also demonstrated. These data support further development of this small-molecule probe for clinical PET of apoptosis.
KW - Apoptosis
KW - Biodistribution
KW - Dosimetry
KW - Molecular imaging
KW - PET
UR - http://www.scopus.com/inward/record.url?scp=79955763128&partnerID=8YFLogxK
U2 - 10.2967/jnumed.110.081786
DO - 10.2967/jnumed.110.081786
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C2 - 21498526
AN - SCOPUS:79955763128
SN - 0161-5505
VL - 52
SP - 720
EP - 725
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 5
ER -