Baris Turkbey1, Maria L Lindenberg2, Stephen Adler3, Karen A Kurdziel2, Yolanda L McKinney2, Juanita Weaver3, Cathy D Vocke4, Miriam Anver3, Gennady Bratslavsky5, Philip Eclarinal3, Gideon Kwarteng3, Frank I Lin2,6, Nana Yaqub-Ogun4, Maria J Merino7, W Marston Linehan4, Peter L Choyke2, Adam R Metwalli8. 1. Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA. turkbeyi@mail.nih.gov. 2. Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA. 3. Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA. 4. Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892-1210, USA. 5. Department of Urology, SUNY Upstate, Syracuse, NY, USA. 6. Cancer Imaging Program, National Cancer Institute, Bethesda, MD, USA. 7. Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. 8. Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892-1210, USA. adam.metwalli@nih.gov.
Abstract
BACKGROUND: Carbonic anhydrase IX (CA-IX) is a potential imaging biomarker of clear cell renal cell carcinoma (ccRCC). Here, we report the results of a phase II clinical trial of a small molecule radiotracer targeting CA-IX ((18)F-VM4-037) in ccRCC. METHODS: Between October 2012 and May 2013, 11 patients with kidney masses underwent (18)F-VM4-037 PET/CT prior to surgery. Dynamic imaging was performed for the first 45 min post injection and whole-body imaging was obtained at 60 min post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging. RESULTS: All patients tolerated the radiotracer well with no adverse events. Ten of the 11 patients had histologically confirmed malignancy. One patient had a Bosniak Type 3 cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors only in the kidney. Primary ccRCC lesions were difficult to visualize on PET alone due to high uptake of the tracer in the adjacent normal kidney parenchyma, however when viewed in conjunction with CT, the tumors were easily localized. Metastatic lesions were clearly visible on PET. Mean SUV for primary kidney lesions was 2.55 in all patients; in patients with histologically confirmed ccRCC, the mean SUV was 3.16. The time-activity curves (TAC) are consistent with reversible ligand binding with peak activity concentration at 8 min post injection followed by washout. Distribution Volume Ratio (DVR) of the lesions was measured using the Logan graphical analysis method. The mean DVR value across the 9 kidney lesions was 5.2 ± 2.8, (range 0.68-10.34). CONCLUSION: 18F-VM4-037 is a well-tolerated PET agent that allows same day imaging of CA-IX expression. The agent demonstrated moderate signal uptake in primary tumors and excellent visualization of CA-IX positive metastases. While the evaluation of primary ccRCC lesions is challenging due to high background activity in the normal kidney parenchyma, 18F-VM4-037 may be most useful in the evaluation of metastatic ccRCC lesions.
BACKGROUND:Carbonic anhydrase IX (CA-IX) is a potential imaging biomarker of clear cell renal cell carcinoma (ccRCC). Here, we report the results of a phase II clinical trial of a small molecule radiotracer targeting CA-IX ((18)F-VM4-037) in ccRCC. METHODS: Between October 2012 and May 2013, 11 patients with kidney masses underwent (18)F-VM4-037 PET/CT prior to surgery. Dynamic imaging was performed for the first 45 min post injection and whole-body imaging was obtained at 60 min post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging. RESULTS: All patients tolerated the radiotracer well with no adverse events. Ten of the 11 patients had histologically confirmed malignancy. One patient had a Bosniak Type 3 cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors only in the kidney. Primary ccRCC lesions were difficult to visualize on PET alone due to high uptake of the tracer in the adjacent normal kidney parenchyma, however when viewed in conjunction with CT, the tumors were easily localized. Metastatic lesions were clearly visible on PET. Mean SUV for primary kidney lesions was 2.55 in all patients; in patients with histologically confirmed ccRCC, the mean SUV was 3.16. The time-activity curves (TAC) are consistent with reversible ligand binding with peak activity concentration at 8 min post injection followed by washout. Distribution Volume Ratio (DVR) of the lesions was measured using the Logan graphical analysis method. The mean DVR value across the 9 kidney lesions was 5.2 ± 2.8, (range 0.68-10.34). CONCLUSION:18F-VM4-037 is a well-tolerated PET agent that allows same day imaging of CA-IX expression. The agent demonstrated moderate signal uptake in primary tumors and excellent visualization of CA-IX positive metastases. While the evaluation of primary ccRCC lesions is challenging due to high background activity in the normal kidney parenchyma, 18F-VM4-037 may be most useful in the evaluation of metastatic ccRCC lesions.
Authors: F Latif; K Tory; J Gnarra; M Yao; F M Duh; M L Orcutt; T Stackhouse; I Kuzmin; W Modi; L Geil Journal: Science Date: 1993-05-28 Impact factor: 47.728
Authors: C R Divgi; N H Bander; A M Scott; J A O'Donoghue; G Sgouros; S Welt; R D Finn; F Morrissey; P Capitelli; J M Williams; D Deland; A Nakhre; E Oosterwijk; S Gulec; M C Graham; S M Larson; L J Old Journal: Clin Cancer Res Date: 1998-11 Impact factor: 12.531
Authors: Matthew H T Bui; David Seligson; Ken-ryu Han; Allan J Pantuck; Frederick J Dorey; Yunda Huang; Steve Horvath; Bradley C Leibovich; Shefali Chopra; Shu-Yuan Liao; Eric Stanbridge; Michael I Lerman; Aarno Palotie; Robert A Figlin; Arie S Belldegrun Journal: Clin Cancer Res Date: 2003-02 Impact factor: 12.531
Authors: William Makis; Anthony Ciarallo; Rajan Rakheja; Stephan Probst; Marc Hickeson; Christopher Rush; Javier-A Novales-Diaz; Vilma Derbekyan; Jerry Stern; Robert Lisbona Journal: Clin Imaging Date: 2012-06-08 Impact factor: 1.605
Authors: E Oosterwijk; N H Bander; C R Divgi; S Welt; J C Wakka; R D Finn; E A Carswell; S M Larson; S O Warnaar; G J Fleuren Journal: J Clin Oncol Date: 1993-04 Impact factor: 44.544
Authors: Bradley C Leibovich; Yuri Sheinin; Christine M Lohse; R Houston Thompson; John C Cheville; Jan Zavada; Eugene D Kwon Journal: J Clin Oncol Date: 2007-10-20 Impact factor: 44.544
Authors: Jean-Jacques Patard; Patricia Fergelot; Pierre I Karakiewicz; Tobias Klatte; Quoc-Dien Trinh; Nathalie Rioux-Leclercq; Jonathan W Said; Arie S Belldegrun; Allan J Pantuck Journal: Int J Cancer Date: 2008-07-15 Impact factor: 7.396
Authors: Nicholas J Farber; Christopher J Kim; Parth K Modi; Jane D Hon; Evita T Sadimin; Eric A Singer Journal: Transl Cancer Res Date: 2017-06 Impact factor: 1.241
Authors: Marlène C Hekman; Mark Rijpkema; Constantijn H Muselaers; Egbert Oosterwijk; Christina A Hulsbergen-Van de Kaa; Otto C Boerman; Wim J Oyen; Johan F Langenhuijsen; Peter F Mulders Journal: Theranostics Date: 2018-03-08 Impact factor: 11.556
Authors: Jean Courcier; Alexandre de la Taille; Maya Nourieh; Ingrid Leguerney; Nathalie Lassau; Alexandre Ingels Journal: Int J Mol Sci Date: 2020-09-28 Impact factor: 5.923