Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan

Sci Rep. 2017 May 11;7(1):1751. doi: 10.1038/s41598-017-01852-8.


There is an ongoing search for new tracers to optimize imaging of beta cell-derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be used for targeting of these tumors. Here, we investigated whether radiolabeled maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively). BALB/c nude mice bearing subcutaneous INS-1 tumors were injected with either In-111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan. Biodistribution studies were carried out at 1, 2 and 4 hours after injection and SPECT/CT imaging 1 and 4 hours after injection of maxadilan-DTPA-111In. Radiolabeling of maxadilan-DTPA (680 MBq/nmol) was more efficient than of DTPA-maxadilan (55 MBq/nmol). Conjugation with DTPA slightly reduced receptor binding affinity in vitro: IC50 values were 3.2, 21.0 and 21.0 nM for maxadilan, natIn-DTPA-maxadilan and maxadilan-DTPA-natIn respectively. Upon i.v. injection maxadilan-DTPA-111In accumulated specifically in INS-1 tumors (7.30 ± 1.87%ID/g) and in the pancreas (3.82 ± 0.22%ID/g). INS-1 tumors were clearly visualized by small animal SPECT/CT. In conclusion, this study showed that the high affinity of maxadilan to the PAC1 receptor was maintained after DTPA conjugation. Furthermore, radiolabeled maxadilan-DTPA accumulated specifically in INS-1 tumors and, therefore, may qualify as a useful tracer to image insulinomas.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Cell Line, Tumor
  • Confidence Intervals
  • Drug Evaluation, Preclinical*
  • Humans
  • Indium Radioisotopes / chemistry
  • Inhibitory Concentration 50
  • Insect Proteins / chemistry
  • Insect Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pentetic Acid / chemistry
  • Radiopharmaceuticals / chemistry
  • Rats
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism*
  • Serum / metabolism
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon


  • Indium Radioisotopes
  • Insect Proteins
  • Radiopharmaceuticals
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • maxadilan protein, insect
  • Pentetic Acid
  • Indium-111