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History of Imaging for Prostate Cancer
Published in Ayman El-Baz, Gyan Pareek, Jasjit S. Suri, Prostate Cancer Imaging, 2018
Prostacint (Cytogen, Princeton NJ), In-111 capromab pendetide, is a radiolabeled antibody targeted to the prostate-specific membrane antigen (PSMA), which is a glycoprotein expressed in both benign and neoplastic prostatic epithelial cells applied clinically in 1996 following FDA approval. It is up-regulated in hormone-resistant states and in metastatic disease (42,43). Unfortunately, Prostacint has limited predictive value in imaging the prostate fossa, particularly following radiation therapy, has low sensitivity for detecting osseous metastasis, and is technically demanding, thus it was not widely adopted (44,45). Novel small molecule imaging PSMA ligands have been developed to attempt to address these limitations. Molecular imaging strategies for evaluating prostate cancer try to capitalize on the increased metabolic needs of cancer cells, tumor-specific expression of androgen receptor membrane proteins, or the osteoblastic reaction adjacent to bone marrow metastasis.
Malignant Neoplasms of the Colon
Published in Philip H. Gordon, Santhat Nivatvongs, Lee E. Smith, Scott Thorn Barrows, Carla Gunn, Gregory Blew, David Ehlert, Craig Kiefer, Kim Martens, Neoplasms of the Colon, Rectum, and Anus, 2007
Moffat et al. (365) assessed the clinical impact of an anti-CEA Fab’ antibody fragment labeled with technetium-99m pertechnetate in 210 patients with advanced or metastatic colorectal carcinoma. When compared with conventional diagnostic modalities, the CEA scan was superior in the extra-hepatic abdomen (55% vs. 32%) and pelvis (69% vs. 48%). Potential clinical benefit was demonstrated in 89 of 210 patients. Corman et al. (366) evaluated the role of immunoscintigraphy with 111Insatumomab pendetide in 103 patients with colorectal carcinoma. In the 84 patients for whom histopathologic information was available, the sensitivity was 73% and the specificity was 100%, with an overall accuracy of 85% for determining the presence and extent of malignant disease. Investigators judged that the antibody imaging mode was a beneficial contribution in 44% and a negative effect in 2% of case studies. Treatment plans were altered in 17 patients.
Radioimmunodetection of Cancer: The Next Dimension
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
David M. Goldenberg, Robert M. Sharkey
The fundamental reason why RAID did not survive beyond about 10 years for most products lies in the images not providing what the clinicians required in terms of information about the disease being studied. Two principal gamma-emitting radionuclides were used, 99mTc and 111In, for planar and single-photon emission computed tomography (SPECT). Although initial imaging studies were performed with purified polyclonal IgG and labeled with 131I (3), murine monoclonal antibodies (mAbs) were adopted quickly and used as either intact IgG or IgG-Fab’ fragments. The target antigens were surface markers on the cancer cells, mostly quantitatively increased as compared with normal tissues and sometimes not accessible by antibody targeting to normal tissues, and mostly glycoproteins integral to the cell membrane or elaborated on and within the cell. Even when elaborated into the circulation, such as for carcinoembryonic antigen (CEA) and other markers, binding to the injected antibody did not prevent tumor localization and imaging, apparently because the antibody was in excess or the binding avidity to circulating antigen was different from that to sessile tumor antigen (4,5). Although most were pancarcinoma antigens, the approved indications were for small cell lung, colorectal, ovarian, and prostatic cancers (2). Except for the prostate cancer–imaging agent, capromab pendetide, all have been removed from the market, being replaced by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. FDG is a metabolic marker for cell proliferation, and therefore provided a means for distinguishing many cancerous lesions from the normal tissues where they were embedded. This sugar analogue is also retained after being taken up by the more metabolically active cells, which includes a number of normal tissues, most notably the brain, heart wall, and bone marrow (6). In contrast to the antibody imaging agents, FDG-PET provided a clearer image distinguishable over background, but importantly too, the registration process for approved clinical use partly circumvented the usual FDA process of proving efficacy by management change, which was required for the RAID products. Since FDG-PET is not reliable in the area of the prostate, the prostatic cancer–imaging agent has been sustained, but only with modest use. The use of 18-fluorine also ushered in the age of PET imaging, a technology within an innate enhanced sensitivity as compared with gamma-imaging systems.
Prostate-specific membrane antigen-directed imaging and radioguided surgery with single-photon emission computed tomography: state of the art and future outlook
Published in Expert Review of Medical Devices, 2022
Luca Filippi, Barbara Palumbo, Viviana Frantellizzi, Susanna Nuvoli, Giuseppe De Vincentis, Angela Spanu, Orazio Schillaci
PSMA is a zinc-containing metal-enzyme transmembrane glycoprotein of type II, that is intensely up-regulated in PC cells with a grade of expression strictly correlated with tumor stage and biological aggressiveness. PSMA’s exact role in prostate normal tissue is still unclear, although it has been hypothesized it might have a trophic function. In past years 111In-capromab pendetide, a monoclonal antibody targeting PSMA, was used for the imaging of PC recurrence and metastases, but it showed limited sensitivity and specificity [32], since this radiocompound recognizes the PSMA-intracytoplasmatic domain that is available only in necrotic or dying tumor cells. Worthy of note, glutamate carboxypeptidase activity is localized in PSMA extracellular domain, thus being exposed to the extracellular space and particularly suitable for theranostic approaches [33].
Piflufolastat F-18 (18F-DCFPyL) for PSMA PET imaging in prostate cancer
Published in Expert Review of Anticancer Therapy, 2022
Andrew F. Voter, Rudolf A. Werner, Kenneth J. Pienta, Michael A. Gorin, Martin G. Pomper, Lilja B. Solnes, Steven P. Rowe
Early efforts to target PSMA for prostate cancer imaging relied on PSMA-specific antibodies. One of the first agents to be developed was 111In-capromab pendetide (ProstaScint), a murine-derived anti-PSMA antibody for SPECT imaging [30]. However, this agent proved less sensitive than 18F-fluciclovine for the detection of metastatic disease [31], likely because the epitope targeted by capromab is sequestered in the intracellular compartment and only becomes accessible to the antibody after disruption of the cell membrane [32,33]. A second-generation antibody conjugate, 89Zr-J591, has been introduced to allow for imaging of intact tumor cells by targeting the extracellular domain of PSMA [24,34]. While this has improved the sensitivity for prostate cancer, 89Zr-J591 requires an extended, week-long imaging delay to allow for adequate tumor uptake, which has hindered its clinical utility [35]. Smaller antibody conjugates with improved pharmacokinetics have been introduced and early clinical trials are underway [36,37].
Long-term outcome of biologically guided dose-escalated radiotherapy of localized prostate cancer
Published in Acta Oncologica, 2022
Anna Kuisma, Pauliina Wright, Sami Suilamo, Jan Seppälä, Mari Koivisto, Paula Lindholm, Heikki Minn
An encouraging 10-year survival rate of 69% (n = 71) was reported by Schild et al. [17] who applied 111In capromab pendetide (ProstaScint) gamma imaging for dose painting of intraprostatic lesion to 82 Gy while the rest of prostate received 75.6 Gy. In line with our study, the incidence of long-term G3-4 toxicity was low. Our corresponding PCa-specific 10-year survival rate of the entire cohort was 86%. Also, Vora et al. reported similar 5-year toxicity rates in IMRT-treated PCa patients who received a mean radiation dose of 75.6 Gy [18]. Pinkawa et al. [19] evaluated survival and long-term toxicity in 383 intermediate- and high-risk PC patients treated with 70.2/1.8 Gy–72/1.8–2.0 Gy. They reported 10-year PC-specific survival of 84%, and biochemical PFS of 78%, respectively, in the 72 Gy subgroup. They also reported the GU and GI toxicity to increase with an increasing follow-up period of 1–10 years.