Interactions of <sup>177</sup>lu-Dotatate With Pharmaceutical Vehicles And Peptides — ASN Events
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  3. Interactions of 177lu-Dotatate With Pharmaceutical Vehicles And Peptides

Interactions of 177lu-Dotatate With Pharmaceutical Vehicles And Peptides (#70)

Irina ROTARU 1 , Rachida LEBTAHI 2 , Nathalie PONS-KERJEAN 1 , Makrem BEN REGUIGA 1
  1. Radiopharmacy Unit - Pharmcy Department - APHP - Hôpital Beaujon, APHP - Hôpital Beaujon, Clichy (92110), France
  2. Nuclear Medicine Department - APHP - Hôpital Beaujon, APHP - Hôpital Beaujon, Clichy (92110), France

Introduction

177Lu-DOTATATE is indicated in neuroendocine tumor Peptide-Receptor Radionuclide Therapy. The therapeutic efficiency and safety of 177Lu-DOTATATE are tightly related to the chelate integrity maintaining until its internalisation in tumour cells. Any alteration on its structure may lead to complex destruction. This may be suspected to occur during co-infusion of pharmaceutical vehicles or in patients receiving cold somatostatin analogues to control their diseases’ symptoms. The aim of this work was to study the physico-chemical interactions of 177Lu-DOTATATE in co-infusion conditions with various current pharmaceutical vehicles and cold somatostatin analogues.

Material and Methods

177Lu-DOTATATE (Lutathera®, AAA, France) was diluted to 1/5th in saline, 5% Glucose, Bicarbonate 8.4%, Ringer-Lactate, octreotide and octreotide LAR, or incubated at 37°C in plasma or plasma enriched with 10% de octreotide. The radiochemical purity was determined by ITLC-SG in 0.1mol/L sodium citrate-pH3. Retention factor (Rf) were: 0.1–0.3 for labelled peptide and Rf=1.0 for Lu3+. RadiochemicalPurity was also determined using C18 Sep-Pak-Plus-Cartridge. Free radionuclide was eluted with 5mL of 0.1mol/L pH3-acetate buffer,labelled peptide with 5mL of methanol and hydroxylated Lu-177 remained inside cartridge. Mixtures were then analyzed immediately, 30min and 24h after dilution. Results were expressed as mean±SD (n= 3-4).

Results and discussion

177Lu-DOTATATE diluted in saline or glucose or cold peptides showed compliant RPC levels during the 24 hours. In Bicarbonate 8.4% and Ringer-Lactate, significant amounts unbound Lutetium were found, respectively 10.5±3.3% and 8.9±4.2%. In plasma mixtures, significant amounts of hydroxylated Lutetium and or unbound lutetium were found 24h incubation: respectively 4.9%±1.3% and 4.2%±0.6% in plasma and respectively 6,3%±1.8% and 4,8%±0.8% in plasma enriched with octreotide. This may due the catalytic activity of plasma which slowly deteriorates the lutated complex. This is unlikely to occur in vivo: 177Lu-DOTATATE is rapidly cleared from the bloodstream within few hours post-infusion.

 

Conclusion

Co-infusion of 177Lu-DOTATATE with alkaline pharmaceutical vehicles may affect the radiopharmaceutical stability and may induceLutetium release.