title: Intratumoral administration of holmium-166 acetylacetonate microspheres: antitumor efficacy and feasibility of multimodality imaging in renal cancer.
abstract: OBJECTIVE
  The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of holmium-166 microspheres ((166)HoAcAcMS). This new technique locally ablates renal tumors through high-energy beta particles, while the gamma rays allow for nuclear imaging and the paramagnetism of holmium allows for MRI.
  
  
  METHODS
  (166)HoAcAcMS were administered intratumorally in orthotopic renal tumors (Balb/C mice). Post administration CT, SPECT and MRI was performed. At several time points (2 h, 1, 2, 3, 7 and 14 days) after MS administration, tumors were measured and histologically analyzed. Holmium accumulation in organs was measured using inductively coupled plasma mass spectrometry.
  
  
  RESULTS
  (166)HoAcAcMS were successfully administered to tumor bearing mice. A striking near-complete tumor-control was observed in (166)HoAcAcMS treated mice (0.10±0.01 cm(3) vs. 4.15±0.3 cm(3) for control tumors). Focal necrosis and inflammation was present from 24 h following treatment. Renal parenchyma outside the radiated region showed no histological alterations. Post administration CT, MRI and SPECT imaging revealed clear deposits of (166)HoAcAcMS in the kidney.
  
  
  CONCLUSIONS
  Intratumorally administered (166)HoAcAcMS has great potential as a new local treatment of renal tumors for surgically unfit patients. In addition to strong cancer control, it provides powerful multimodality imaging opportunities.
authors: Imaging Division, Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Wouter
authors: W
authors: Bult
authors: Stephanie G C
authors: SG
authors: Kroeze
authors: Mattijs
authors: M
authors: Elschot
authors: Peter R
authors: PR
authors: Seevinck
authors: Freek J
authors: FJ
authors: Beekman
authors: Hugo W A M
authors: HW
authors: de Jong
authors: Donald R A
authors: DR
authors: Uges
authors: Jos G W
authors: JG
authors: Kosterink
authors: Peter R
authors: PR
authors: Luijten
authors: Wim E
authors: WE
authors: Hennink
authors: Alfred D
authors: AD
authors: van het Schip
authors: J L H Ruud
authors: JL
authors: Bosch
authors: J Frank W
authors: JF
authors: Nijsen
authors: Judith J M
authors: JJ
authors: Jans
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D005240:Feasibility Studies; D006695:Holmium / Q000008:administration & dosage* / Q000627:therapeutic use; D006885:Hydroxybutyrates / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D064847:Multimodal Imaging; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D010422:Pentanones / Q000008:administration & dosage; D049268:Positron-Emission Tomography; D011868:Radioisotopes / Q000008:administration & dosage* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006885:Hydroxybutyrates; D009942:Organometallic Compounds; D010422:Pentanones; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C049529:acetyl acetonate; D006695:Holmium