title: VPAC1 receptors for imaging breast cancer: a feasibility study.
abstract: VPAC1 encodes G-protein-coupled receptors expressed on all breast cancer (BC) cells at the onset of the disease, but not on benign lesions. Our extensive preclinical studies have shown that (64)Cu-TP3805 has a high affinity for VPAC1, is stable in vivo, and has the ability to distinguish spontaneously grown malignant BC masses from benign lesions. Our long-term goal is to develop (64)Cu-TP3805 as an agent to perform in vivo histology, to distinguish malignant lesions from benign masses noninvasively and thereby avoid patient morbidity and the excess economic costs of benign biopsies.
  
  
  METHODS
  (18)F-FDG obtained commercially served as a control. (64)Cu-TP3805 was prepared using a sterile kit containing 20 μg of TP3805. Radiochemical purity and sterility were examined. Nineteen consenting women with histologically proven BC were given 370 MBq of (18)F-FDG. One hour later, 6 of these patients were imaged with PET/CT and 13 with positron emission mammography (PEM). Two to 7 d later, 6 PET/CT patients received 111 MBq (± 10%) (n = 2), 127 MBq (± 10%) (n = 2), or 148 MBq (± 10%) (n = 2) of (64)Cu-TP3805 and were imaged 2 and 4 h later. Thirteen PEM patients received 148 MBq (± 10%) of (64)Cu-TP3805 and were imaged 15 min, 1 h, 2 h, and 4 h later. Standardized uptake value (SUV) was calculated for PET/CT patients, and PUV/BGV (PEM uptake value/background value) was calculated for PEM patients. Tumor volume was also calculated.
  
  
  RESULTS
  The radiochemical purity of (64)Cu-TP3805 was 97% ± 2%, and specific activity was 44.4 GBq (1.2 Ci)/μmol. In 19 patients, a total of 24 lesions were imaged (15 invasive ductal carcinoma, 1 high-grade mammary carcinoma, 3 lobular carcinoma, 1 invasive papilloma, and 4 sentinel lymph nodes). All lesions were unequivocally detected by (64)Cu-TP3805 and by (18)F-FDG. The average tumor volume as determined by PET/CT with (64)Cu-TP3805 was 90.6% ± 16.1% of that with (18)F-FDG PET/CT, and the average SUV was 92% ± 26.4% of that with (18)F-FDG. For PEM, the tumor volume with (64)Cu-TP3805 was 113% ± 37% of that with (18)F-FDG and the PUV/BGV ratio was 97.7% ± 24.5% of that with (18)F-FDG.
  
  
  CONCLUSIONS
  (64)Cu-TP3805 is worthy of further investigation in patients requiring biopsy of suggestive imaging findings, to further evaluate its ability to distinguish malignant lesions from benign masses noninvasively.
authors: Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. mathew.thakur@jefferson.edu
authors: Mathew L
authors: ML
authors: Thakur
authors: Kaijun
authors: K
authors: Zhang
authors: Adam
authors: A
authors: Berger
authors: Barbara
authors: B
authors: Cavanaugh
authors: Sung
authors: S
authors: Kim
authors: Chaitra
authors: C
authors: Channappa
authors: Andrea J
authors: AJ
authors: Frangos
authors: Eric
authors: E
authors: Wickstrom
authors: Charles M
authors: CM
authors: Intenzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D003301:Copper Radioisotopes; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D019275:Radiopharmaceuticals; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I
keywords: 64Cu-TP3805 for PEM; 64Cu-TP3805 for PET; in vivo histology; targeting VPAC1
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