PSMA diagnostics and treatments of prostate cancer become mature

Eyben, Finn Edler von; Baumann, G.; Baüm, Richard

doi:10.1007/s40336-018-0270-2

Cited by 25 publications

(22 citation statements)

References 24 publications

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“…The poor life expectancy of this group likely masks the emergence of late radiationinduced kidney failure, which generally requires 2 or more years to manifest (35). However, renal toxicity might become a more significant concern if PSMA-RLT were to be initiated in patients at an early stage of (high risk) PCa with (oligo)-metastatic disease (36). A protection approach to meaningfully mitigate toxicities associated with PSMA radiotherapeutics would be useful to enable the broadest, earliest and most effective use of these radiotherapeutics.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Monosodium Glutamate on PSMA Radiotracer Uptake in Men with Recurrent Prostate Cancer: A Prospective, Randomized, Double-Blind, Placebo-Controlled Intraindividual Imaging Study

et al. 2020

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The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [ 18 F]DCFPyl PET/CT imaging sessions were performed 3-7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P=0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P=0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P=0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P=0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range-1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [ 18 F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

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Section: Discussionmentioning

confidence: 99%

The Effects of Monosodium Glutamate on PSMA Radiotracer Uptake in Men with Recurrent Prostate Cancer: A Prospective, Randomized, Double-Blind, Placebo-Controlled Intraindividual Imaging Study

et al. 2020

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“…Second to lung cancer, prostate cancer is the most life-threatening cancer among American males, with an estimate of 29,430 deaths in 2018 73, 74. The selection of appropriate targets is a critical step in the development of BiTEs; prostate-specific membrane antigen (PSMA) is one of the ideal candidates, which is highly expressed in prostate adenocarcinoma and plays an underlying role in the progression of prostate cancer 75, 76. Despite the different PSMA-specific bsAbs developed up to now, the particular features of BAY2010112 (also known as MT111, AMG 212, or pasotuxizumab), an anti-PSMA BiTE antibody designed by Friedrich et al 73 .…”

Section: Main Textmentioning

confidence: 99%

Single-Chain Variable Fragment-Based Bispecific Antibodies: Hitting Two Targets with One Sophisticated Arrow

Ahamadi-Fesharaki

Fateh

Vaziri

et al. 2019

Molecular Therapy - Oncolytics

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Despite the success of monoclonal antibodies (mAbs) to treat some disorders, the monospecific molecular entity of mAbs as well as the presence of multiple factors and pathways involved in the pathogenesis of disorders, such as various malignancies, infectious diseases, and autoimmune disorders, and resistance to therapy have restricted the therapeutic efficacy of mAbs in clinical use. Bispecific antibodies (bsAbs), by concurrently recognizing two targets, can partly circumvent these problems. Serial killing of tumor cells by bsAb-redirected T cells, simultaneous blocking of two antigens involved in the HIV-1 infection, and concurrent targeting of the activating and inhibitory receptors on B cells to modulate autoimmunity are part of the capabilities of bsAbs. After designing and developing a large number of bsAbs for years, catumaxomab, a full-length bsAb targeting EpCAM and CD3, was approved in 2009 to treat EpCAM-positive carcinomas besides blinatumomab, a bispecific T cell engager antibody targeting CD19 and CD3, which was approved in 2014 to treat relapsed or refractory acute lymphoblastic leukemia. Furthermore, approximately 60 bsAbs are under investigation in clinical trials. The current review aims at portraying different formats of the single-chain variable fragment (scFv)-based bsAbs and shedding light on the scFv-based bsAbs in preclinical development, different phases of clinical trials, and the market.

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“…3 Radiolabelled PSMA ligands (Ga-68 and F-18) -of all available prostate cancer PET agents, PSMA ligands represent the biggest advance. [3][4][5][6][7][8] These are receptor agents (rather than metabolic markers) that bind to a surface transmembrane glycoprotein.…”

Section: F-18 Labelled Fluciclovine (Axumin)mentioning

confidence: 99%