Dosimetric model for locoregional treatments of brain tumors with 90Y-conjugates: clinical application with 90Y-DOTATOC.
Locoregional (LR) administration of (90)Y-conjugates after surgical debulking is a promising therapeutic option of gliomas. Dosimetry is highly recommended, as patient-specific parameters influence the absorbed dose to target and normal tissues. After tumor resection, the absorbed dose must be carefully evaluated in the rim of tissue surrounding the resected area. The aim of this study was to calculate and provide the S values, according to the MIRD concept, for dosimetry of LR brain treatments with several (90)Y-labeled compounds. The S values thus obtained have been clinically applied in 12 patients treated with (90)Y-labeled [DOTA(0),D-Phe(1),Tyr(3)]octreotide ((90)Y-DOTATOC).


METHODS
An anthropomorphic model for Monte Carlo simulations was developed to evaluate absorbed doses in brain-adjacent tissue (BAT) and in normal brain. To adapt the model to single patients, S values were evaluated taking into account (i) different surgical resection cavity (SRC) volumes, (ii) different percentages of conjugate binding to the cavity wall, and (iii) different depths of percolation of the conjugate trough the cavity wall. BAT was divided into 1-mm-thick consecutive adjacent shells to evaluate the dose distribution around the cavity. Corresponding S values were obtained to allow dosimetric evaluation in brain LR therapy with (90)Y-conjugates. In the clinical treatments, 0.4-1.1 GBq of (90)Y-DOTATOC were injected into the SRC via an appropriate catheter. The activity in the SRC was assumed to be the difference between the total injected activity and the activity in the blood plus the activity cumulatively eliminated with the urine.


RESULTS
Assuming no diffusion, with a mean residence time in SRC of 60 +/- 8 h, absorbed doses to shell II were 0.25 and 0.03 Gy/MBq for SRC volumes of 7.2 and 65.4 mL, respectively. Assuming a slight diffusion of 1 mm with a 7.2-mL SRC, absorbed dose to shells I, II, and VI were consistently different: 5.32, 2.53, and 0.12 Gy/MBq, respectively. Mean doses to normal brain, red marrow, bladder wall, and total body were 0.015, 0.03, 1.22, and 0.006 MGy/MBq.


CONCLUSIONS
The model proved to be suitable for the dosimetry of several LR therapies with (90)Y-conjugates. According to our results, LR treatment with (90)Y-DOTATOC can safely deliver very high doses to target tissue, sparing normal organs including brain.
Ferrari
Mahila
M
Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy.
Cremonesi
Marta
M
Bartolomei
Mirco
M
Bodei
Lisa
L
Chinol
Marco
M
Fiorenza
Maurizio
M
Tosi
Giampiero
G
Paganelli
Giovanni
G
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D011881:Radiotherapy, Computer-Assisted / Q000379:methods; D012062:Relative Biological Effectiveness
D019275:Radiopharmaceuticals; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide