title: Individual voxelwise dosimetry of targeted 90Y-labelled substance P radiotherapy for malignant gliomas.
abstract: OBJECTIVE
  Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently overexpressed in malignant gliomas. The peptidic vector 111In/90Y-DOTAGA-substance P binds to these receptors and can be used for local treatment of brain tumours. Dosimetry for this interstitial brachytherapy has mainly been done using geometrical models; however, they often do not faithfully reproduce the in vivo biodistribution of radiopharmaceuticals, which is indispensable to correlate the deposited energy with clinical response. The aim of this study was to establish a reproducible dosimetry protocol for intratumoural radiopeptide therapy.
  
  
  METHODS
  For test and therapeutic injections, 2 MBq of 111In-substance P and 370-3,330 MBq of 90Y-substance P, respectively, were applied in 12 patients with malignant gliomas. Over a period of 24 h, serial SPECT scans were performed on a dual-head SPECT camera. The scans were acquired in a double-energy window technique together with 99mTc-ECD in order to co-register the dose distributions with a separately acquired, contrast-enhanced CT scan. Quantitative voxelwise dose distribution maps (in Gy/GBq) were computed from these data using a mono-exponential decay approach. Pre- and post-therapeutic values were compared.
  
  
  RESULTS
  Agreement between pre- and post-therapeutic dosimetry was very good and delivered absolute dose values in Gy per injected GBq. In all patients, the pretherapeutic test injection together with the CT overlay technique could predict the precise localisation of dose deposition in an anatomical context.
  
  
  CONCLUSIONS
  This protocol allows a precise pretherapeutic computation of the expected three-dimensional dose distribution and is clearly superior to the previously used dosimetry based on planar scintigraphic images. It has become an indispensable tool for planning intratumoural radiopeptide therapy in glioma patients.
authors.affiliation: Clinic and Institute for Nuclear Medicine, University Hospital Basel, Basel, Switzerland. skneifel@uhbs.ch
authors.forename: Stefan
authors.initials: S
authors.lastname: Kneifel
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
authors.forename: Helena
authors.initials: H
authors.lastname: Uusijärvi
authors.forename: Stephan
authors.initials: S
authors.lastname: Good
authors.forename: Ludwig
authors.initials: L
authors.lastname: Plasswilm
authors.forename: Carlos
authors.initials: C
authors.lastname: Buitrago-Téllez
authors.forename: Jan
authors.initials: J
authors.lastname: Müller-Brand
authors.forename: Helmut
authors.initials: H
authors.lastname: Mäcke
authors.forename: Adrian
authors.initials: A
authors.lastname: Merlo
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D008962:Models, Theoretical; D011874:Radiometry / Q000379:methods*; D011878:Radiotherapy / Q000379:methods; D012044:Regression Analysis; D013373:Substance P / Q000737:chemistry*; D014057:Tomography, X-Ray Computed; D015021:Yttrium Radioisotopes
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D008024:Ligands; D015021:Yttrium Radioisotopes; D013373:Substance P