title: Phase 2 Study of99mTc-Trofolastat SPECT/CT to Identify and Localize Prostate Cancer in Intermediate- and High-Risk Patients Undergoing Radical Prostatectomy and Extended Pelvic LN Dissection.
abstract: 99mTc-trofolastat (99mTc-MIP-1404), a small-molecule inhibitor of prostate-specific membrane antigen, shows high potential to detect prostate cancer (PCa) noninvasively using SPECT. We therefore wanted to assess the performance of99mTc-trofolastat SPECT/CT in a phase 2 multicenter, multireader prospective study in patients with intermediate- and high-grade PCa, before radical prostatectomy and extended pelvic lymph node (LN) dissection, with histopathology as the gold standard.Methods:PCa patients (n= 105) with an increased risk of LN involvement (LNI) underwent pelvic99mTc-trofolastat SPECT/CT before radical prostatectomy with extended pelvic LN dissection. The sensitivity of99mTc-trofolastat for detection of PCa on a patient and lobe basis, using visual and semiquantitative (tumor-to-background ratio [TBR]) scores, and of LNI was evaluated as well as the correlation of uptake within the gland to Gleason scores (GS) and assessment of the predictive potential of99mTc-trofolastat uptake for LNI.Results:PCa was detected in 98 patients (94%) with acceptable variability between readers. There was a significantly higher visual score and TBR in positive lobes compared with tumor-negative lobes. Receiver-operating characteristic analysis showed that visual scores more accurately discriminated lobes with GS ≤ 3 + 3 from ≥ 3 + 4, whereas TBRs discriminated high-grade disease from normal lobes better. Visual scores and TBRs correlated significantly with GS.99mTc-trofolastat SPECT/CT detected LNI with a sensitivity of 50% and specificity of 87%, and TBR values significantly predicted LNI with a sensitivity of 90%.Conclusion:99mTc-trofolastat SPECT/CT detects PCa with high sensitivity in patients with intermediate- and high-risk PCa compared with histology. It has the potential to be used as a surrogate marker for GS and predict LNI.
authors.affiliation: Nuclear Medicine, UZ Leuven, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium Karolien.goffin@uzleuven.be.
authors.forename: Karolien E
authors.initials: KE
authors.lastname: Goffin
authors.affiliation: Urology, UZ Leuven, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.affiliation: Jahn Ferenc South Pest Hospital, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Tenke
authors.affiliation: University of Texas Vanguard Urologic Institute, Houston, Texas.
authors.forename: Kevin
authors.initials: K
authors.lastname: Slawin
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: Progenics Pharmaceuticals, New York, New York; and.
authors.forename: Nancy
authors.initials: N
authors.lastname: Stambler
authors.affiliation: Progenics Pharmaceuticals, New York, New York; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Strack
authors.affiliation: Weill Cornell Medicine, New York, New York.
authors.forename: John
authors.initials: J
authors.lastname: Babich
authors.affiliation: Progenics Pharmaceuticals, New York, New York; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Armor
authors.affiliation: Progenics Pharmaceuticals, New York, New York; and.
authors.forename: Vivien
authors.initials: V
authors.lastname: Wong
mesh_terms: D000368:Aged; D001692:Biological Transport; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds / Q000378:metabolism; D010388:Pelvis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery*; D012306:Risk; D000072098:Single Photon Emission Computed Tomography Computed Tomography
chemical_list: D015609:Organotechnetium Compounds; C000595576:technetium 99m 1-(1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)-9,14-dioxo-2,8,13,15-tetraazaoctadecane-7,12,16,18-tetracarboxylic acid)
keywords: 99mTc-trofolastat (99mTc-MIP-1404); SPECT/CT; histopathology; prostate cancer