Biodistribution and dosimetry of 99mTc-BTAP-annexin-V in humans

Abstract

The purpose of this study was to determine the biodistribution and the associated radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V (99mTc-Apomate), a tracer proposed for the study of apoptosis. Eight patients (including two females) with normal kidney and liver functions were included in the study. An activity of 580 +/- 90 MBq of 99mTc-Apomate was injected intravenously, immediately followed by a dynamic study of 30 frames of 1 min each. At about 1 h, 4 h and 20 h p.i., whole-body scans were acquired. All activity distributions were measured using a dual-head gamma camera. Before injection of activity, a transmission scan with a cobalt-57 flood source had been performed to determine patient attenuation. Blood samples were taken every 10 min during the first hour after injection, and at about 4 and 20 h. Urine and faeces were collected during the first 20 h. Organ uptake was estimated after correction for body background activity, attenuation and scatter. Residence times were calculated from the dynamic and whole-body studies and used as input in the Mirdose 3.1 program to obtain organ doses and effective dose. It was found that radioactivity strongly accumulated in the kidneys and the liver [at 70 min p.i., 28% +/- 8% and 20% +/- 4% of the injected dose (ID), respectively]. Uptake in the target tissues (lymphomas or heart) was negligible from a dosimetric point of view. Extrapolating data from the first 20 h, one finds that approximately 73% of the ID will be excreted in the urine, and 27% in the faeces. The biological half-life of the activity in the total body was 16 +/- 7 h. Some organ doses +/- standard deviation (SD) in microGy/MBq were: kidneys 63 +/- 22, urinary bladder 20 +/- 6, spleen 15 +/- 3, liver 13 +/- 3, upper large intestine 12 +/- 6, lower large intestine 8 +/- 4, testes 6 +/- 2 and red bone marrow 4 +/- 0.7. The effective dose was 7.6 +/- 0.5 microSv/MBq, corresponding to a total effective dose of 4.6 +/- 0.3 mSv for a nominal injected activity of 600 MBq. In conclusion, 99mTc-Apomate has a high uptake in the kidneys and liver--in fact a factor of 1.3-1.6 higher than that found for the previously studied 99mTc-(n-1-imino-4-mercaptobutyl)-annexin-V. The biological half-life is shorter, however, but still long compared with the physical half-life of 99mTc. The faster appearance of activity in the intestines may preclude imaging of apoptosis in the abdomen. The effective dose is within the lower range of values reported for typical 99mTc compounds.

18F-ICMT-11, a Caspase-3–Specific PET Tracer for Apoptosis: Biodistribution and Radiation Dosimetry

“…The biodistribution study of 18 F-ML-10, a small-molecule apoptotic tracer, demonstrated a distinct pattern of uptake in the testes (27). However, the biodistribution studies of annexin-Vbased radiotracers ( 99m Tc-annexin-V, 99m Tc-hydrazino nicotinate [HYNIC]-annexin-V, and 99m Tc-4, 5-bis [thioacetoamide] pentanoyl [BTAP]-annexin-V) did not show increased uptake in the testes, with the absorbed dose in the testes ranging from 0.005 to 0.015 mGy/MBq (28)(29)(30). This dose is comparable to the absorbed testes dose observed with 18 F-ICMT-11 (0.007 mGy/MBq).…”

99mTc-Annexin-V Uptake in a Rat Model of Variable Ischemic Severity and Reperfusion Time

“…[11][12][13][14][15] In addition, investigation of the biodistribution and dosimetry of various forms of radiolabeled annexin in human subjects has demonstrated the Circulation Journal Vol.71, July 2007 safety of this agent, as well as the efficacy of imaging for the detection of acute myocardial infarction (MI) and cardiac transplant rejection. [16][17][18][19][20] In patients with MI, there is intense localization of 99m TcAnnexin-V in the infarct region, both in patients with and those without reperfusion, 18,21 which suggests that a considerable number of cells in the infarct zone die by apoptosis. 22,23 Although the most effective method of limiting the zone of injury in areas of markedly decreased perfusion is restoration of blood flow, experimental studies have demonstrated that reperfusion is a major stimulus for apoptosis in previously ischemic tissue, especially in nonsalvageable cells.…”

“…[16][17][18][19][20] In patients with MI, there is intense localization of 99m TcAnnexin-V in the infarct region, both in patients with and those without reperfusion, 18,21 which suggests that a considerable number of cells in the infarct zone die by apoptosis. 22,23 Although the most effective method of limiting the zone of injury in areas of markedly decreased perfusion is restoration of blood flow, experimental studies have demonstrated that reperfusion is a major stimulus for apoptosis in previously ischemic tissue, especially in nonsalvageable cells.…”

Apoptosis-reactivating agents for targeted anticancer therapy

“…Выявление апоптотических клеток с помощью ОФЭКТ основано на визуализации молекул анионного липида фосфатидилсерина (которые экспонированы на поверхности апоптотических, но не интактных клеток) с помощью радиофармпрепарата, содержащего белок аннексин V. В 1998 г. были получены первые аннексиновые зонды, меченные 99m Tc [57]. Результаты клинических испытаний указанных радиофармпрепаратов свидетельствуют о хорошей переносимости процедуры их внутривенного введения и отсутствии побочных эффектов [58,59]. Период полувыведения из организма 99m Tc-аннексина V составляет 62±13 ч. Проведена вторая фаза клинических испытаний 99m Tc-HYNIC-аннексина V с целью визуализации апоптоза у 16 больных немелкоклеточным раком лёгкого после начала лечения комбинацией цисплатины и гемцитабина [60].…”