title: First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer.
abstract: This phase 1 study was performed to determine the pharmacokinetics and ability to visualize prostate cancer in bone, soft-tissue, and the prostate gland using (123)I-MIP-1072 and (123)I-MIP-1095, novel radiolabeled small molecules targeting prostate-specific membrane antigen.
  
  
  METHODS
  Seven patients with a documented history of prostate cancer by histopathology or radiologic evidence of metastatic disease were intravenously administered 370 MBq (10 mCi) of (123)I-MIP-1072 and (123)I-MIP-1095 2 wk apart in a crossover trial design. (123)I-MIP-1072 was also studied in 6 healthy volunteers. Whole-body planar and SPECT/CT imaging was performed and pharmacokinetics studied over 2-3 d. Target-to-background ratios were calculated. Absorbed radiation doses were estimated using OLINDA/EXM.
  
  
  RESULTS
  (123)I-MIP-1072 and (123)I-MIP-1095 visualized lesions in soft tissue, bone, and the prostate gland within 0.5-1 h after injection, with retention beyond 48 h. Target-to-background ratios from planar images averaged 2:1 at 1 h, 3:1 at 4-24 h, and greater than 10:1 at 4 and 24 h for SPECT/CT. Both agents cleared the blood in a biphasic manner; clearance of (123)I-MIP-1072 was approximately 5 times faster. (123)I-MIP-1072 was excreted in the urine, with 54% and 74% present by 24 and 72 h, respectively. In contrast, only 7% and 20% of (123)I-MIP-1095 had been renally excreted by 24 and 72 h, respectively. Estimated absorbed radiation doses were 0.054 versus 0.110 mGy/MBq for the kidneys and 0.024 versus 0.058 mGy/MBq for the liver, for (123)I-MIP-1072 and (123)I-MIP-1095, respectively.
  
  
  CONCLUSIONS
  (123)I-MIP-1072 and (123)I-MIP-1095 detect lesions in soft tissue, bone, and the prostate gland at as early as 1-4 h. These novel radiolabeled small molecules have excellent pharmacokinetic and pharmacodynamic profiles and warrant further development as diagnostic and potentially when labeled with (131)I therapeutic radiopharmaceuticals.
authors.affiliation: Molecular Insight Pharmaceuticals, Inc, Cambridge, Massachusetts 02142, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Barrett
authors.forename: R Edward
authors.initials: RE
authors.lastname: Coleman
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
authors.forename: Shankar
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: Neil A
authors.initials: NA
authors.lastname: Petry
authors.forename: Steve
authors.initials: S
authors.lastname: Cho
authors.forename: Thomas
authors.initials: T
authors.lastname: Armor
authors.forename: James B
authors.initials: JB
authors.lastname: Stubbs
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Maresca
authors.forename: Michael G
authors.initials: MG
authors.lastname: Stabin
authors.forename: John L
authors.initials: JL
authors.lastname: Joyal
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: John W
authors.initials: JW
authors.lastname: Babich
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D005971:Glutamates / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014508:Urea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: C544834:2-(3-(1-carboxy-5-(3-(4-iodobphenyl)ureido)pentyl)ureido)pentanedioic acid; C544833:2-(3-(1-carboxy-5-(4-iodobenzylamino)pentyl)ureido)pentanedioic acid; D005971:Glutamates; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D014508:Urea