Characterization of the [(153)Sm]Sm-EDTMP pharmacokinetics and estimation of radiation absorbed dose on an individual basis.
[(153)Sm]Sm-EDTMP is a radiopharmaceutical used in palliation cares of bone metastases. The purpose of this study is to provide an explicit description of [(153)Sm]Sm-EDTMP pharmacokinetics, adopting a simple three-compartmental model with the analytical expressions calculating the rate constants and determining biodistribution parameters, like radiopharmaceutical uptake and clearance. This biokinetic model allowed us to calculate on an individual basis the dose to bone surface and to red bone marrow and to assess the degree of variability in dosimetric parameters using a fixed administered activity based only on patient weight. In this study twenty patients were enrolled and were treated with [(153)Sm]Sm-EDTMP, administering a fixed activity per kilogram (37 MBq/kg); blood and urine samples were collected during 24 h post treatment. The median value of the administered activity was 2.7 GBq. Blood clearance confirmed that an aliquot of [(153)Sm]Sm-EDTMP rapidly localizes and is retained in bone, while the remainder is rapidly cleared from the blood pool by the urinary system. Our data show a bi-exponential clearance from blood: the rapid component has a half life median value of 6 min (range: 2-24 min), while the slow one has a half life median value of 1.4 h (range: 0.6-5.8 h). Median value of the urinary excretion is 40 (range: 3-75) % of the administered activity. Our model shows the behaviour of a tracer which is distributed in the extracellular space of the body, localized in the skeleton and excreted via glomerular filtration. Half life median values of [(153)Sm]Sm-EDTMP transferring between compartments, T(1/2) (blood→ECF), T(1/2) (ECF→blood) are 7.4 (range: 1.9-37) and 48 (range: 8-408) min, respectively. Median values of half lives of [(153)Sm]Sm-EDTMP clearance through the urine and of uptake into bone are 1.0 (range: 0.1-6.0) and 1.6 (range: 0.6-9.0) h, respectively. Median value of red marrow absorbed dose is 2.1 (range: 0.7-3.5) Gy and 0.8 (range: 0.3-2.1) Gy/GBq, while median value of bone surface absorbed dose is 11.5 Gy (range: 5.0-18.4) and 4.4 (range: 2.3-14.3) Gy/GBq. It is remarkable that there is a really great biological variability within patients, especially considering the excreted activity. The cumulated activity in bone and red marrow doses were significantly higher in prostate cancer, where metastatic bone lesions are osteoblastic, than in breast cancer where metastatic bone lesions are osteolytic or mixed (lytic/blastic). The relevant biological variability in biodistribution and metabolism of [(153)Sm]Sm-EDTMP suggests that the fixed administered activity based on patient weight is not sufficient to optimize the treatment and a better optimization would be reached by using a predictive dosimetry tailored to individual patient characteristics.
Vigna
L
L
Medical Physics Department; Azienda Ospedaliera Maggiore della Carità, C.so Mazzini 18, 28100 Novara, Italy.
Matheoud
R
R
Ridone
S
S
Arginelli
D
D
Della Monica
P
P
Rudoni
M
M
Inglese
E
E
Brambilla
M
M
D000465:Algorithms; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects; D001859:Bone Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C061972:samarium Sm-153 lexidronam