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Evaluation of a B-cell leukemia-lymphoma 2-specific radiolabeled peptide nucleic acid–peptide conjugate for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma

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  • 1 Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 2 Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 3 Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 4 Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 5 Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of Missouri, Columbia, MO 65211.
  • | 6 Division of Animal Sciences, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, MO 65211.
  • | 7 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
  • | 8 Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 9 Harry S. Truman Memorial Veterans' Hospital, 800 Hospital Dr, Columbia, MO 65201.
  • | 10 Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 11 Harry S. Truman Memorial Veterans' Hospital, 800 Hospital Dr, Columbia, MO 65201.

Abstract

Objective—To evaluate use of a radiolabeled peptide nucleic acid–peptide conjugate (RaPP) targeting B-cell leukemia-lymphoma 2 (BCL2) mRNA for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma and to assess associations among RaPP uptake, time to tumor progression (TTP), and BCL2 mRNA expression.

Animals—11 dogs with B-cell lymphoma and 1 clinically normal dog.

Procedures—Scintigraphic images were acquired 1 hour after IV injection of the RaPP. Regions of interest (ROIs) were drawn around lymph nodes, liver, and spleen; ROI intensity (relative to that of an equally sized region of muscle in the same image) was measured. Each ROI was also subjectively categorized as positive or negative for increased RaPP uptake. Expression of BCL2 mRNA was determined via quantitative reverse transcriptase PCR assay of a lymph node sample from dogs with lymphoma. Associations among imaging results, TTP, and BCL2 mRNA expression were evaluated.

Results—Increased RaPP uptake was detected in affected tissues of dogs with lymphoma. Dogs with superficial cervical lymph node ROIs categorized as negative (n = 8) for increased RaPP uptake had a significantly longer TTP than did dogs for which this ROI was considered positive (2). Measured intensity of mandibular and superficial cervical lymph node ROIs was negatively associated with TTP. Associations among BCL2 mRNA and ROI intensity or TTP were not significant.

Conclusions and Clinical Relevance—Increased RaPP uptake at mandibular or superficial cervical lymph node ROIs may be a negative prognostic indicator in dogs with lymphoma. A larger investigation is needed to determine clinical value of the RaPP for disease detection and prognostication.

Contributor Notes

Supported by National Institutes of Health Grant No. CA103130 and Veterans Administration Grant No. BX000575.

Address correspondence to Dr. Lewis (LewisMic@missouri.edu).