Ultrasensitive time-resolved immunofluorometric assay of prostate-specific antigen in serum and preliminary clinical studies

1993 ◽  
Vol 39 (10) ◽  
pp. 2108-2114 ◽  
Author(s):  
H Yu ◽  
E P Diamandis

Abstract We developed an ultrasensitive method for measuring prostate-specific antigen (PSA) in serum. The assay includes a capture monoclonal anti-PSA antibody coated to microtiter wells, a biotinylated rabbit polyclonal detection antibody, and alkaline phosphatase (ALP)-labeled streptavidin. The activity of ALP is measured with the substrate diflunisal phosphate; the released diflunisal forms highly fluorescent complexes with Tb(3+)-EDTA that are quantified with microsecond time-resolved fluorometry. The assay is precise and accurate and correlates well with the established Hybritech Tandem-PSA kit. Its distinguishing feature is extreme sensitivity (lowest limit of detection is 0.002 micrograms/L or 2 x 10(6) PSA molecules per assay). This is the most sensitive PSA assay reported thus far; we used it to quantify PSA in patients who had undergone radical prostatectomy. Many patients had < 0.01 micrograms/L PSA in their serum. This method could have important clinical applications in postsurgical early detection of relapse or residual prostate cancer, as recently suggested in the literature (Clin Chem 1992;38:1930-2).

1993 ◽  
Vol 149 (4) ◽  
pp. 787-792 ◽  
Author(s):  
Thomas A. Stamey ◽  
Howard C.B. Graves ◽  
Nancy Wehner ◽  
Michelle Ferrari ◽  
Fuad S. Freiha

2020 ◽  
Vol 66 (10) ◽  
pp. 1329-1338
Author(s):  
Annie H Ren ◽  
Antoninus Soosaipillai ◽  
Anu Mathew ◽  
Galina Nikolenko ◽  
Laukik Sardesai ◽  
...  

Abstract Background We investigated an ultrasensitive prostate-specific antigen (uPSA) immunoassay (MesoScale; lower limit of detection (LLD) of 0.0035 pg/mL) to monitor patients with prostate cancer (PCa) following radical prostatectomy (RP) and to examine whether changes in PSA in the conventionally undetectable range (<1 pg/mL) can predict biochemical relapse (BCR). Methods We measured uPSA in serial serum samples (N = 100) collected from 20 RP cases with a third-generation ELISA (LLD of 1 pg/mL) and the fifth-generation MesoScale assay. We analyzed the PSA nadir changes to classify patients into BCR or non-BCR groups, observed the trends in PSA kinetics, and associated BCR status with clinicohistopathological features. Results The ELISA could quantify PSA in only 38% of the RP samples, detecting BCR in 7 of 20 patients with PCa. The MesoScale assay quantified PSA in all samples, showing 8 of 20 patients with BCR. However, there was no significant difference between the median time to BCR detection based on ELISA (1016 days) compared with MesoScale data (949 days). Gleason scores were higher in the BCR groups compared with non-BCR. There was no significant difference for other clinicohistopathological parameters. Conclusions The uPSA MesoScale technology could track miniscule changes in serum PSA in the range of 0.003–1 pg/mL in all RP cases. However, PSA kinetics and nadir at concentrations <2 pg/mL fluctuated, and increases below this range could not reliably suggest signs of BCR. Instead, ultrasensitive fifth-generation PSA assays may hold clinical potential for measuring the low concentrations of PSA in women for various medical contexts.


Urology ◽  
2002 ◽  
Vol 60 (4) ◽  
pp. 31-35 ◽  
Author(s):  
Wolfgang Horninger ◽  
Carol D Cheli ◽  
Richard J Babaian ◽  
Herbert A Fritsche ◽  
Herbert Lepor ◽  
...  

2006 ◽  
Vol 176 (2) ◽  
pp. 559-563 ◽  
Author(s):  
Shomik Sengupta ◽  
Carl M. Christensen ◽  
Horst Zincke ◽  
Jeffrey M. Slezak ◽  
Bradley C. Leibovich ◽  
...  

2013 ◽  
Vol 3 (3) ◽  
pp. 213 ◽  
Author(s):  
Stéphane Bolduc ◽  
Brant A. Inman ◽  
Louis Lacombe ◽  
Yves Fradet ◽  
Roland R. Tremblay

Purpose: We assessed the role of urinary prostate-specific antigen(uPSA) in the follow-up of prostate cancer after retropubic radicalprostatectomy (RRP) for the early detection of local recurrences.Methods: We recruited 50 patients previously treated for prostatecancer with RRP and who had not experienced a prostatespecificantigen (PSA) recurrence within their first postoperativeyear into a cross-sectional laboratory assessment and prospective6-year longitudinal follow-up study. We defined biochemicalfailure as a serum PSA (sPSA) of 0.3 μg/L or greater. Patientsprovided blood samples and a 50-mL sample of first-voided urine.We performed Wilcoxon rank-sum and Fisher exact tests for statisticalanalysis.Results: The median sPSA was 0.13 μg/L. The median uPSA was0.8 μg/L, and was not significantly different when comparingGleason scores or pathological stages. Of the 50 patients, 27 initiallyhad a nondetectable sPSA but a detectable uPSA, and11 patients experienced sPSA failure after 6 years. Six patients haddetectable sPSA and uPSA initially. Fifteen patients were negativefor both sPSA and uPSA, and 13 remained sPSA-free after 6 years.The odds ratio (OR) of having sPSA failure given a positive uPSAtest was 4.5 if sPSA was undetectable, but was reduced to 2.6 ifsPSA was detectable. The pooled Mantel–Haenszel OR of 4.2 suggestedthat a detectable uPSA quadrupled the risk of recurrence,independent of whether sPSA was elevated or not. The sensitivityof uPSA for detecting future sPSA recurrences was 81% andspecificity was 45%.Conclusion: Urinary PSA could contribute to an early detection oflocal recurrences of prostate cancer after a radical prostatectomy.Objectif : Nous avons évalué le rôle de l’antigène prostatiquespécifique (APS) urinaire dans le suivi du cancer de la prostateaprès prostatectomie radicale rétropubienne (PRR) pour le dépistageprécoce de récidives locales.Méthodes : Cinquante patients atteints de cancer de la prostatetraités par PRR et n’ayant présenté aucune récidive avec anomaliede l’APS dans l’année suivant l’intervention chirurgicale ontété inscrits à une étude transversale par épreuves de laboratoireavec suivi longitudinal prospectif sur 6 ans. L’échec sur le planbiochimique était défini comme un taux d’APS sérique de 0,3 μg/Lou plus. Les patients devaient fournir des échantillons de sanget un échantillon d’urine du matin de 50 mL. Les analyses statistiquesreposaient sur le test de Wilcoxon et la méthode exactede Fisher.Résultats : La valeur médiane de l’APS sérique était de 0,13 μg/L.La valeur médiane de l’APS urinaire était de 0,8 μg/L; la différenceétait non significative quand on tenait compte des scores deGleason ou des stades pathologiques. Sur les 50 patients,27 présentaient des taux d’APS sérique non décelables au début,mais des taux d’APS urinaire décelables; 11 patients ont présentéun échec quant aux taux d’APS sérique après 6 ans. Six patientsavaient des taux d’APS sérique et urinaire décelables au départ.Quinze patients n’avaient aucun taux décelable d’APS sérique ouurinaire, et aucun APS sérique n’était toujours décelable chez13 patients après 6 ans. Le rapport de risque d’un échec quantaux taux d’APS sérique après détection d’APS urinaire est de 4,5en l’absence d’un taux d’APS sérique décelable, mais diminueà 2,6 en présence d’un taux d’APS sérique décelable. Le rapportde risque cumulé de 4,21 calculé par la méthode deMantel–Haenszel porte à croire que des taux d’APS urinaire décelablesquadruplent le risque de présenter une récidive, queles taux sériques soient élevés ou non. La sensibilité du test dedépistage de l’APS urinaire pour la détection des récidives avecanomalie des taux sériques était de 81 %, et la spécificité, de 45 %.Conclusion : Le taux d’APS urinaire peut contribuer à un dépistageprécoce des récidives locales après une prostatectomie radicale.


2015 ◽  
Vol 33 (1) ◽  
pp. 16.e1-16.e7 ◽  
Author(s):  
Heikki Seikkula ◽  
Kari T. Syvänen ◽  
Samu Kurki ◽  
Tuomas Mirtti ◽  
Pekka Taimen ◽  
...  

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