Pathologic correlation of 89Zr-Df-IAB2M antiprostate-specific membrane antigen (PSMA) minibody in patients with metastatic prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 220-220 ◽  
Author(s):  
Michael J. Morris ◽  
Stephen Barnett Solomon ◽  
Jeremy C. Durack ◽  
Joseph A. O' Donoghue ◽  
Serge K. Lyashchenko ◽  
...  

220 Background: IAB2M is a novel anti-PSMA minibody (Mb) based on the humanized J591 antibody that targets the extracellular domain of PSMA. The Mb has been engineered to remove Fc-Rn interactions and reduce the molecular weight relative to J591. The result is faster blood pool clearance, for a more favorable imaging schedule, while retaining bivalent targeting of PSMA. We have previously reported on the pharmacokinetics, dosimetry, and lesion uptake of IAB2M(Pandit-Taskar et al, WMIS 2014). Here we report the correlation between imaging and pathology of biopsies of PSMA avid lesions. Methods: Following standard imaging (SI) of CT/MRI, bone scintigraphy (BS), and FDG PET, 5 mCi of 89Zr-Df-IAB2M was administered intravenously. Escalating minibody doses of 10, 20, and 50 mg were delivered, with cohort expansion at 10 and 20 mg. Whole body PET/CT scans were serially performed at various time points:1-2 h, 24 h, 48 h, and 72-144 h post injection. Metastases identified on PET were confirmed, where possible, with bx’s in the following preference: concordant IAB2M and FDG positivity, IAB2M, and FDG mismatch, or a mismatch between SI and any PET. Results: 24 patients (pts) with metastatic prostate cancer were scanned (11 at 10, 7 at 20, and 6 at 50 mg Mb doses). A total of 15 bxs (7 soft tissue, 8 bone) were performed on 14 pts; the histopathologic correlation is summarized in the table below. 13 lesions were identified by IAB2M, 11 by FDG, and 14 by SI. Of these, 12/13 (92.3%), 10/11 (90.9%), 12/14 (85.7%) were biopsy positive for cancer, respectively. 2 bone lesions were not identified by IAB2M, evident on other imaging modalities, and were both neg by bx. Overall bx concordance (pos/pos, neg/neg) with imaging was: IAB2M 14/15 (93%) vs. BS/CT 13/15 (86%) vs. FDG 12/15 (80%). Conclusions: An ongoing analysis of IAB2M imaging showed a high concordance with pathologic findings in patients with metastatic prostate cancer. Clinical trial information: NCT01923727. [Table: see text]

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 144-144
Author(s):  
Martin Boegemann ◽  
Axel Semjonow ◽  
Hans-Joerg Breyholz ◽  
Andres Jan Schrader ◽  
Laura-Maria Krabbe ◽  
...  

144 Background: Recently developed 68Ga labeled prostate specific membrane antigen (PSMA) ligands were introduced as diagnostic tools to detect prostate cancer (PCa), PCa relapse and metastases with high accuracy. In this study we assessed the usability of preoperative PSMA-PET/CT information on congruency of spread of PCA compared with postoperative PCa-maps derived from radical prostatectomy (RPE) specimens. Methods: We referred 6 patients with biopsy proven high risk PCa to PSMA-PET/CT prior to RPE. Whole body PET/CT (Biograph mCT with 128 slice CT, Siemens) was performed 62±8 minutes after injection of 160±31 MBq [68Ga]-PSMA-HBED-CC (DKFZ-Ga-PSMA-11) as described by routine acquisition protocol. After RPE, prostate specimens were processed in the local pathology department. Topographical analysis of extension of PCa was reconstructed from representative slides on a schematic diagram resulting in a PCa-map of the prostate. After aligning the cutting planes of the PSMA-PET/CT to the PCa-map we defined 20 segments of the prostate and the seminal vesicles. We measured the maximum standard uptake value (SUV) of PSMA activity of the respective segments and compared the concordance of PSMA-positive and -negative areas with those of PCa and no PCa on the PCa-maps. We calculated sensitivity, specificity, positive and negative likelihood ratios (LR) taking available segments into account. Results: 106/112 segments were analyzed. 8 segments were excluded due to spillover of PSMA-activity in bladder urine. All but 3 segments with no PCa on the PCa-maps showed no uptake in PSMA-PET/CT (Specificity = 92%). The sensitivity of PSMA-PET/CT for showing PCa areas was equally 92%. The positive and negative LR for PSMA-PET/CT detecting or ruling out PCa was 11.5 and 0.09, respectively. Conclusions: This preliminary proof of concept study shows that prediction of later pathologic results in RPE-specimens could be estimated by preoperative PSMA-PET/CT. With optimized acquisition protocols it may be possible to improve our preliminary results. Perspectively PSMA-PET/CT may be helpful for identifying PCa suspicious lesions prior to prostate biopsy and support decision making prior to RPE or radiation therapy.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 231-231
Author(s):  
Farhad Fakhrejahani ◽  
Maria Liza Lindenberg ◽  
Ethan S. Bargvall ◽  
Esther Mena ◽  
Baris Turkbey ◽  
...  

231 Background: Conventional imaging of advanced prostate cancer (computerized tomography and nuclear bone scintigraphy) is limited and indicates a need for a more specific molecular imaging probe. DCFBC is a radiolabeled PET agent that binds with high affinity to prostate specific membrane antigen (PSMA), which is overexpressed in almost all prostate cancers and through whole-body non-invasive functional imaging, may provide new information on the expression of PSMA. We compare the uptake of DCFBC in bone with respect to NaF PET/CT in metastatic prostate cancer patients. DCFBC has added capability to detect soft tissue metastasis whereas NaF is confined to secondary effects of bone disease. Methods: Subjects with known or suspected prostate cancer metastasis underwent DCFBC PET/CT imaging performed at 1 hour and 2 hours after IV bolus injection of 8 mCi of DCFBC. Patients also underwent a whole body NaF PET/CT scan within 3 weeks of DCFBC PET/CT to assess for bone metastases. Patients received 3 mCi of NaF IV bolus and then were imaged 1hour post injection. PSA levels and antiandrogen therapy status were obtained at the time of DCFBC imaging. Results: Fifteen patients have been preliminarily analyzed. PSA ranged from < .01 to 4379 ng/mL. NaF identified bone lesions in 10 patients but matching focal DCFBC uptake was only seen in 3 patients. DCFBC additionally showed lymph node metastasis in 1of these 3 patient. There were 5 patients without focal abnormal bone uptake on NaF or DCFBC. In this group, 4 of 5 patients had focal DCFBC uptake in lymph nodes or soft tissue lesions. Ten patients were on some form of androgen deprivation therapy (ADT). For those on ADT, 7 of 10 patients had positive findings on NaF, compared to 2 of 10 patients on DCFBC. Conclusions: DCFBC uptake in bone metastasis does not routinely correspond to focal NaF uptake which could be due to distinct mechanisms of tracer uptake and tumor biology. There is an inverse association in focal bone findings when comparing each tracer on antiandrogen therapy. Through whole-body non-invasive functional imaging and further study, DCFBC may prove useful in characterizing prostate cancer based on PSMA expression. Clinical trial information: NCT02190279.


2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Jochen Greiner ◽  
Rainer Küfer ◽  
Sven N. Reske ◽  
Volker Martin ◽  
Hartmut Döhner ◽  
...  

The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11) C-Choline positron emission tomography/computerized tomography (PET/CT). After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 . The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.


2018 ◽  
Vol 43 (7) ◽  
pp. 509-511 ◽  
Author(s):  
Hayden A. Snow ◽  
Michael S. Hofman ◽  
Catherine A. Mitchell ◽  
David E. Gyorki ◽  
Myles J.F. Smith

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5093-TPS5093
Author(s):  
Michael J. Morris ◽  
Frederic Pouliot ◽  
Lawrence Saperstein ◽  
Steven P. Rowe ◽  
Michael A. Gorin ◽  
...  

TPS5093 Background: Early and accurate detection of recurrent or metastatic prostate cancer remains an unmet diagnostic need for patient management. While agents for positron emission tomography (PET), such as 11C-choline and 18F-fluciclovine, have emerged as options for imaging recurrent prostate cancer, these agents are not specific for the disease. 18F-DCFPyL is a novel, low-molecular weight, PET radiopharmaceutical that binds selectively to prostate-specific membrane antigen with high affinity. In prior studies, 18F-DCFPyL PET/CT has shown reliable diagnostic performance in detecting metastatic or recurrent prostate cancer (Rowe Mol Imaging Biol 2016 18:411-19; Gorin J Urol 2018 1999:126-32). Methods: CONDOR is a phase 3, multicenter, open-label study designed to assess the diagnostic performance and clinical impact of 18F-DCFPyL PET/CT in men with suspected recurrent or metastatic prostate cancer. Approximately 200 patients are planned to be enrolled across 15 centers in the United States and Canada. Eligible patients ≥18 years of age must have histologically confirmed prostate adenocarcinoma, have rising PSA after definitive therapy, and negative or equivocal conventional imaging. A single 9 mCi (333 MBq) dose of 18F-DCFPyL is administered, followed by whole body PET/CT scan 1 hour later. The primary objective is to assess the correct localization rate (percentage of patients with a one-to-one correspondence between localization of at least one lesion identified on 18F-DCFPyL PET/CT and the composite truth standard, defined as either evaluable histopathology, informative correlative imaging, or PSA response after radiation therapy). Additional study objectives include safety and tolerability of 18F-DCFPyL, impact on intended treatment plans, detection rates and PPV of 18F-DCFPyL by region, and detection rates by baseline PSA. 18F-DCFPyL PET/CT results are centrally reviewed by independent readers blinded to all clinical and other imaging information. As of February 9, 2019, a total of 36 patients have been dosed in the study. Clinical trial information: NCT03739684.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Sotirios Chondrogiannis ◽  
Maria Cristina Marzola ◽  
Gaia Grassetto ◽  
Anna Margherita Maffione ◽  
Lucia Rampin ◽  
...  

Purpose. (1) To evaluate a new acquisition protocol of18F-choline (FCH) PET/CT for prostate cancer patients (PC), (2) to review acquisition18F-choline PET/CT methodology, and (3) to propose a standardized acquisition protocol on FCH PET/CT in PC patients.Materials. 100 consecutive PC patients (mean age 70.5 years, mean PSA 21.35 ng/mL) were prospectively evaluated. New protocol consisted of an early scan of the pelvis immediately after the injection of the tracer (1 bed position of 4 min) followed by a whole body scan at one 1 hour. Early and 1 hour images were compared for interfering activity and pathologic findings.Results. The overall detection rate of FCH PET/CT was 64%. The early static images of the pelvis showed absence of radioactive urine in ureters, bladder, or urethra which allowed a clean evaluation of the prostatic fossae. Uptake in the prostatic region was better visualized in the early phase in 26% (7/30) of cases. Other pelvic pathologic findings (bone and lymph nodes) were visualized in both early and late images.Conclusion. Early18F-choline images improve visualization of abnormal uptake in prostate fossae. All pathologic pelvic deposits (prostate, lymph nodes, and bone) were visualized in both early and late images.


2018 ◽  
Vol 64 (6) ◽  
pp. 799-804
Author(s):  
Darya Ryzhkova ◽  
M. Poyda

Purpose: To study the diagnostic value of PET-CT with 68Ga-PSMA-11 in the diagnosis of a primary prostate cancer, preoperative staging, and the detection of recurrence of prostate cancer (PCa). Methods: 28 patients aged 64.7 ± 8.74 years were included. 10 patients primary prostate cancer, and 18 patients with biochemical recurrence of the disease after radical treatment were examined. All patients underwent PET-CT with 68Ga-PSMA-11 according the whole body protocol. Interpretation of images was performed visually and quantitatively by calculation of SUL max. Results: High focal or diffuse 68Ga-PSMA-11 uptake was found in prostate parenchyma in patients with primary prostate cancer. Additionally metastases in regional lymph nodes were diagnosed in 4 patients and bone metastases were found in one patient. The correlation between 68Ga-PSMA-11 uptake level and Gleason index in the primary tumor (R Spearmen = 0.25, p = 0.57) was not observed. PET-positive results were obtained in 14 patients and PET-negative results in 4 patients with biochemical recurrence of PCa. The relationship between the frequency of PET-positive results and Gleason index was not revealed (R Spearmen = 0.2, p = 0.39). We found a weak but significant correlation between the frequency of PET-positive results and the prostate tumor stage according to the T category (R Spearmen = 0.49, p = 0.049). In patients with low values of PSA (less than 1.0 ng/ml) in 4 out of 9 cases, PET-negative results were obtained. In patients with PSA level more than 1.0 ng/ml PET-positive results were obtained in all cases. Conclusions: PET/CT with 68Ga-PSMA-11 allows to diagnose the primary prostate cancer, to establish the stage of the disease in categories N and M, and also to determine the localization and dissemination of the tumor in patients with biochemical recurrence of prostate cancer. The relationship between 68Ga-PSMA-11 uptake in primary tumor and Gleason index was not found. The probability of obtaining PET-positive results in cases of biochemical recurrence is affected by a PSA level above 1 ng/ml and a high stage of the disease according to the T category (T3-T4).


Author(s):  
Olwen Westerland ◽  
◽  
Ashik Amlani ◽  
Christian Kelly-Morland ◽  
Michal Fraczek ◽  
...  

Abstract Purpose Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma. Methods Forty-six patients undergoing 18F-FDG PET/CT and WBMRI were reviewed by a nuclear medicine physician and radiologist, respectively, for the presence of myeloma bone disease. Blinded clinical and imaging data were reviewed by two haematologists in consensus and management recorded following clinical data ± 18F-FDG PET/CT or WBMRI. Bone disease was defined using International Myeloma Working Group (IMWG) criteria and a clinical reference standard. Per-patient sensitivity for lesion detection was established. McNemar test compared management based on clinical assessment ± 18F-FDG PET/CT or WBMRI. Results Sensitivity for bone lesions was 69.6% (32/46) for 18F-FDG PET/CT (54.3% (25/46) for PET component alone) and 91.3% (42/46) for WBMRI. 27/46 (58.7%) of cases were concordant. In 19/46 patients (41.3%) WBMRI detected more focal bone lesions than 18F-FDG PET/CT. Based on clinical data alone, 32/46 (69.6%) patients would have been treated. Addition of 18F-FDG PET/CT to clinical data increased this to 40/46 (87.0%) patients (p = 0.02); and WBMRI to clinical data to 43/46 (93.5%) patients (p = 0.002). The difference in treatment decisions was not statistically significant between 18F-FDG PET/CT and WBMRI (p = 0.08). Conclusion Compared to 18F-FDG PET/CT, WBMRI had a higher per patient sensitivity for bone disease. However, treatment decisions were not statistically different and either modality would be appropriate in initial staging, depending on local availability and expertise.


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