Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen-Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer.

PURPOSE: The Prostate Imaging Reporting and Data System (PI-RADS) score is standard of care for clinically significant prostate cancer (csPCa) diagnosis. The PRIMARY score (prostate-specific membrane antigen [PSMA]-positron emission tomography [PET]/CT) also has high diagnostic accuracy for csPCa. This study aimed to develop an easily calculated combined (P) score for csPCa detection (International Society of Urological Pathology [ISUP] ≥2) incorporating separately read PI-RADS and PRIMARY scores, with external validation. MATERIALS AND METHODS: Two datasets of men with suspected PCa, no prior biopsy, recent MRI and 68Ga-PSMA-11-PET/CT, and subsequent transperineal biopsy were evaluated. The development sample (n = 291, 56% csPCa) a prospective trial and the validation sample (n = 227, 67% csPCa) a multicenter retrospective database. Primary outcome was detection of csPCa (ISUP ≥2), with ISUP ≥ 3 cancer detection a secondary outcome. Score performance was evaluated by area under the curve, sensitivity, specificity, and decision curve analysis. RESULTS: The 5-point combined (P) score was developed in a prospective dataset. In the validation dataset, csPCa was identified in 0%, 20%, 52%, 96%, and 100% for P score 1 to 5. The area under the curve was 0.93 (95% CI: 0.90-0.96), higher than PI-RADS 0.89 (95% CI: 0.85-0.93, P = .039) and PRIMARY score alone 0.84 (95% CI: 0.79-0.89, P < .001). Splitting scores at 1/2 (negative) vs 3/4/5 (positive), P score sensitivity was 94% (95% CI: 89-97) compared to PI-RADS 89% (95% CI: 83-93) and PRIMARY score 86% (95% CI: 79-91). For ISUP ≥ 3, P score sensitivity was 99% (95% CI: 95-100) vs 94% (95% CI: 88-98) and 92% (95% CI: 85-97) for PI-RADS and PRIMARY scores respectively. A maximum standardized uptake value > 12 (P score 5) was ISUP ≥ 2 in all cases with 93% ISUP ≥ 3. CONCLUSIONS: The P score is easily calculated and improves accuracy for csPCa over both PI-RADS and PRIMARY scores. It should be considered when PSMA-PET is undertaken for diagnosis.

The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology: A single centre retrospective study.

Objective: To review the risk of prostate cancer (PCa) in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) ordered at Department of Urology, The Wesley Hospital, Brisbane, QLD, Australia for non-PCa related pathology. Methods: Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted. Men were classified as benign, indeterminate, or malignant depending of the results of prostate-specific antigen (PSA), PSA velocity, biopsy histopathology, and three-Tesla (3 T) multiparametric MRI (mpMRI) Prostate Imaging Reporting and Data System score, or gallium-68-prostate-specific membrane antigen (68Ga-PSMA) PET/CT results. Results: Three percent (273/9122) of men demonstrated 18F-FDG avidity within the prostate. Eighty-five percent (231/273) were further investigated, including with PSA tests (227/231, 98.3%), 3 T mpMRI (68/231, 29.4%), 68Ga-PSMA PET/CT (33/231, 14.3%), and prostate biopsy (57/231, 24.7%). Results were considered benign in 130/231 (56.3%), indeterminate in 31/231 (13.4%), and malignant in 70/231 (30.3%). PCa was identified in 51/57 (89.5%) of the men who proceeded to biopsy, including 26/27 (96.3%) men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/CT. The most common Gleason score on biopsy was greater than or equal to 4+5 (14/51, 27.5%). 68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33 (78.8%). All 13 men with a positive concordant 18F-FDG, 3 T mpMRI, and 68Ga-PSMA PET/CT had PCa on biopsy. There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups (5.7 vs. 6.1; p=0.580). Conclusion: In this study, after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT, 70 of the 231 cases (30.3%; 0.8% of the entire cohort) had results consistent with PCa, most commonly as Gleason score greater than or equal to 4+5 disease. Unless there is limited life expectancy due to competing medical co-morbidity, men with an incidental finding of intraprostatic uptake on 18F-FDG should be further investigated using principles of PCa detection.

Reproducibility and Accuracy of the PRIMARY Score on PSMA PET and of PI-RADS on Multiparametric MRI for Prostate Cancer Diagnosis Within a Real-World Database.

The PRIMARY score is a 5-category scale developed to identify clinically significant intraprostate malignancy (csPCa) on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT (68Ga-PSMA PET) using a combination of anatomic site, pattern, and intensity. Developed within the PRIMARY trial, the score requires evaluation in external datasets. This study aimed to assess the reproducibility and diagnostic accuracy of the PRIMARY score in a cohort of patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET before prostate biopsy for the diagnosis of prostate cancer. Methods: In total, data from 242 men who had undergone 68Ga-PSMA PET and mpMRI before transperineal prostate biopsy were available for this ethics-approved retrospective study. 68Ga-PSMA PET and mpMRI data were centrally collated in a cloud-based deidentified image database. Six experienced prostate-focused nuclear medicine specialists were trained (1 h) in applying the PRIMARY score with 30 sample images. Six radiologists experienced in prostate mpMRI read images as per the Prostate Imaging-Reporting and Data System (PI-RADS), version 2.1. All images were read (with masking of clinical information) at least twice, with discordant findings sent to a masked third (or fourth) reader as necessary. Cohen κ was determined for both imaging scales as 5 categories and then collapsed to binary (negative and positive) categories (score 1 or 2 vs. 3, 4, or 5). Diagnostic performance parameters were calculated, with an International Society of Urological Pathology grade group of at least 2 (csPCa) on biopsy defined as the gold standard. Combined-imaging-positive results were defined as any PI-RADS score of 4 or 5 or as a PI-RADS score of 1-3 with a PRIMARY score of 3-5. Results: In total, 227 patients with histopathology, 68Ga-PSMA PET, and mpMRI imaging before prostate biopsy were included; 33% had no csPCa, and 67% had csPCa. Overall interrater reliability was higher for the PRIMARY scale (κ = 0.70) than for PI-RADS (κ = 0.58) when assessed as a binary category (benign vs. malignant). This was similar for all 5 categories (κ = 0.65 vs. 0.48). Diagnostic performance to detect csPCa was comparable between PSMA PET and mpMRI (sensitivity, 86% vs. 89%; specificity, 76% vs. 74%; positive predictive value, 88% vs. 88%; negative predictive value, 72% vs. 76%). Using combined imaging, sensitivity was 94%, specificity was 68%, positive predictive value was 86%, and negative predictive value was 85%. Conclusion: The PRIMARY score applied by first-user nuclear medicine specialists showed substantial interrater reproducibility, exceeding that of PI-RADS applied by mpMRI-experienced radiologists. Diagnostic performance was similar between the 2 modalities. The PRIMARY score should be considered when interpreting intraprostatic PSMA PET images.

Primary tumour PSMA intensity is an independent prognostic biomarker for biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: The prognostic value of PSMA intensity on PSMA PET/CT due to underlying biology and subsequent clinical implications is an emerging topic of interest. We sought to investigate whether primary tumour PSMA PET intensity contributes to pre- and post-operative prediction of oncological outcomes following radical prostatectomy. METHODS: We performed a retrospective cohort study of 848 men who underwent all of multiparametric MRI (mpMRI), transperineal prostate biopsy, and 68 Ga-PSMA PET/CT prior to radical prostatectomy. PSMA intensity, quantified as maximum standard uptake value (SUVmax), and other clinical variables were considered relative to post-operative biochemical recurrence-free survival (BRFS) using Cox regression and Kaplan-Meier analysis. RESULTS: After a median follow-up of 41 months, 219 events occurred; the estimated 3-year BRFS was 79% and the 5-year BRFS was 70%. Increasing PSMA intensity was associated with less favourable BRFS overall (Log rank p < 0.001), and within subgroups of Gleason score category (Log rank p < 0.03). PSMA intensity was significantly associated with shorter time to biochemical recurrence, after adjusting for pre-operative (HR per 5-unit SUVmax increase = 1.15) and post-operative (HR per 5-unit SUVmax increase = 1.10) parameters. CONCLUSION: These results in a large series of patients confirm PSMA intensity to be a novel, independent prognostic factor for BRFS.

Prognostic significance of morphological patterns of Gleason grade 5 prostatic adenocarcinoma diagnosed on needle biopsy.

Grading is one of the best prognostic indicators of prostate cancer with Gleason grade 5 having the worst outcome. The prognostic influence of grade 5 patterns remains uncertain. A total of 646 prostate needle biopsy sets with Gleason score (GS) 9-10 prostatic adenocarcinoma were prospectively analysed. Patterns of grade 5 were correlated with radical prostatectomy (RP) adverse findings of high tumour volume (TV), extra-prostatic extension (EPE), seminal vesicle invasion (SVI) and lymph node involvement (LNI) in 472 and biochemical recurrence (BCR) in 338 patients after RP. Mean age and serum PSA were 69 years (range 37-91) and 26.1 ng/mL (range 1.4-1800), respectively. Gleason scores were 4+5=9 in 539 (83%), 5+4=9 in 94 (15%) and 5+5=10 in 13 cases (2%). Clusters/cords, single cells, sheets and comedocarcinoma were found in 86%, 69%, 26% and 18% with a pure pattern in 25% of cases. Comparing cases with and without sheets, there were no significant differences with RP high TV (p=0.8577), EPE (p=0.5372), SVI (p=0.5183) and LNI (p=0.4323). However, the presence of sheets predicted a significantly higher BCR rate (p=0.0033), while for tumours with single cells, the interval to BCR was significantly shorter (p<0.0001). Comparing cases with and without the other patterns, two other significant differences were found. Comedocarcinoma predicted high TV (p=0.0230) and single cells predicted EPE (p=0.0101). This study shows that all patterns currently used to assign a Gleason grade 5, including sheets, comedocarcinoma, single cells and clusters/cords, are associated with aggressive outcomes validating their inclusion in grade 5.

Histological comparison between predictive value of preoperative 3-T multiparametric MRI and 68 Ga-PSMA PET/CT scan for pathological outcomes at radical prostatectomy and pelvic lymph node dissection for prostate cancer.

OBJECTIVE: To evaluate the ability of preoperative multiparametric magnetic resonance imaging (mpMRI) and a gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) scan to predict pathological outcomes and also identify a group of men with a <5% risk of histological pelvic lymph node metastasis (LNM) at pelvic lymph node dissection (PLND) performed during a robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer. We then aimed to compare these results to known risk calculators for LNM, including the Cancer of the Prostate Risk Assessment (CAPRA) score, Memorial Sloan Kettering Cancer Centre (MSKCC) and Briganti nomograms. PATIENTS AND METHODS: Between July 2014 and September 2019 only men who had both a preoperative mpMRI and staging 68 Ga-PSMA PET/CT at our institution followed by a RALP with PLND referred to a single specialist uropathology laboratory were considered for inclusion. The data were collected retrospectively prior to February 2019 and in a prospective manner thereafter. A model was built to allocate probabilities of the men with a negative 68 Ga-PSMA PET/CT scan having a <5% risk of histologically LNM at RALP based on the preoperative radiological staging. RESULTS: A total of 233 consecutive men met the inclusion criteria of which 58 men (24.9%) had a LNM identified on PLND histology. The median (range) International Society of Urological Pathology (ISUP) Grade was 5 (1-5) and the median (range) prostate-specific antigen level was 7.4 (1.5-72) ng/mL. The median (range) number of resected lymph nodes was 16 (1-53) and the median (range) number of positive nodes identified on histology was 2 (1-22). Seminal vesicle invasion on mpMRI was more common in node-positive men than in the absence of LNM (31% vs 12%). The maximum standardised uptake value of the primary tumour on 68 Ga-PSMA PET/CT was higher in men with LNM (median 9.2 vs 7.2, P = 0.02). Suspected LNM were identified in 42/233 (18.0%) men with 68 Ga-PSMA PET/CT compared with 22/233 (9.4%) men with mpMRI (P = 0.023). The positive and negative predictive value for 68 Ga-PSMA PET/CT was 66.7% and 84.3% respectively, compared to 59.1% and 78.7% for mpMRI. A predictive model showed only two men (4.2%) with a negative preoperative 68 Ga-PSMA PET/CT would be positive for a histological LNM if they are ISUP Grade < 5 and Prostate Imaging-Reporting and Data System (PI-RADS) <5; or ISUP Grade 5 with PI-RADS < 4. An inspection of three additional variables: CAPRA score, MSKCC and Briganti nomograms did not improve the predictive probability for this group. However, of the 61 men with ISUP Grade 4-5 malignancy and also a PI-RADS 5 mpMRI, 20 (32.8%) men had a microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT. CONCLUSION: Preoperative 68 Ga-PSMA/PET CT was more sensitive in identifying histological pelvic LNM than 3-T mpMRI. Men with a negative 68 Ga-PSMA PET/CT have a lower risk of LNM than predicted with CAPRA scores or MSKCC and Briganti nomograms. We identified that the combination of a negative preoperative 68 Ga-PSMA PET/CT, ISUP biopsy Grade <5 and PI-RADS <5 prostate mpMRI, or an ISUP Grade 5 with PI-RADS <4 on mpMRI was associated with a <5% risk of a LNM. The addition of CAPRA scores, MSKCC and Briganti nomograms did not improve the predictive probability within this model. Conversely, men with ISUP Grade 4-5 malignancy associated with a PI-RADS 5 prostate mpMRI had a >30% risk of microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT and this high-risk group would appear suitable for an extended PLND at the time of a radical prostatectomy.

Histological findings of totally embedded robot assisted laparoscopic radical prostatectomy (RALP) specimens in 1197 men with a negative (low risk) preoperative multiparametric magnetic resonance imaging (mpMRI) prostate lobe and clinical implications.

BACKGROUND: Prostate multiparametric magnetic resonance imaging (mpMRI) has become a popular initial investigation of an elevated PSA and is being incorporated into active surveillance protocols. Decisions on prostate cancer investigation and management based solely on a normal mpMRI remains controversial. Histopathological findings of a totally embedded normal mpMRI lobe are rarely described. METHODS: A retrospective review of the histological findings of negative preoperative mpMRI lobes in men treated by robot assisted laparoscopic radical prostatectomy (RALP). Inclusion criteria included a preoperative low risk mpMRI for both lobes (Prostate Imaging-Reporting and Data System (PIRADS) ≤ 2) or one negative lobe (with a PIRADS 3-5 in the opposite lobe). RESULTS: A single normal mpMRI lobe was identified in 1018 men (PIRADS 3-5 group). Both lobes were normal in 179 men (PIRADS ≤ 2 group). Prostate cancer was identified in 47.6% (485/1018) of the normal mpMRI lobe opposite a PIRADS 3-5 lesion, including 13.2% (134/1018) with >0.5 cc of International Society of Urologic Pathologists (ISUP) grade 2, or a higher grade cancer. ISUP grade 4-5 was only identified in 2% (20/1018). Compared to RALP histology of the PIRADS 3-5 mpMRI tumour, a pathological ISUP upgrade in the normal mpMRI lobe was identified in 58/1018 men (5.7%). In the PIRADS ≤ 2 group extraprostatic extension occurred in 19% (34/179) and seminal vesicle invasion (pT3b) in 3.9% (7/179). There was no difference in margin status between the PIRADS 3-5 and ≤2 groups (p = 0.247). CONCLUSIONS: mpMRI underestimates tumour grade and volume compared to totally embedded histopathological analysis of RALP specimens, although ISUP grade 4-5 cancer is uncommon. Our analysis provides useful insight into the multifocality of prostate cancers, and highlights the utility of systematic biopsy, in addition to targeted biopsies. These results have ramifications for clinical decisions on prostate cancer management based solely on the mpMRI appearance, including active surveillance.

Solitary rib lesions showing prostate-specific membrane antigen (PSMA) uptake in pre-treatment staging 68 Ga-PSMA-11 positron emission tomography scans for men with prostate cancer: benign or malignant?

OBJECTIVES: To determine the proportion of solitary rib lesions on pre-treatment 68 Gallium-labelled prostate-specific membrane antigen (PSMA)/computed tomography (CT) scans in men with prostate cancer that are malignant and examine any predictive factors. PATIENTS AND METHODS: This retrospective single tertiary referral institution cohort study of men reviewed the results of 68 Ga-PSMA-11 positron emission tomography (PET)/CT scans performed for primary staging prior to treatment of prostate cancer from July 2014 to September 2019. Men with PSMA uptake outside the prostate in only the rib lesion were included. A solitary rib lesion was considered to be malignant if it increased in size on follow-up imaging. A lesion was considered benign if the prostate-specific antigen (PSA) level remained <0.1 µg/L following a radical prostatectomy (RP), <2 µg/L above nadir following radiotherapy (RT) as per the Phoenix criteria, histology was benign on rib biopsy, or follow-up imaging showed no growth of the rib lesion. If a lesion did not meet these criteria it was considered indeterminate. RESULTS: A total of 62 men had PSMA uptake in a solitary rib lesion; 54 went on to have RPs and eight underwent RT. In all, 61 of the men (98.4%) met the criteria for a benign rib lesion. Only one man had a false-negative malignant lesion. This man had a rib lesion with a low maximum standardised uptake value (SUVmax ) of 2.21 reported as benign, but the postoperative PSA level was 0.67 µg/L and the rib lesion progressed on follow-up imaging, with development of widespread metastases. Of the benign rib lesions, there were four false positives reported as possible metastases. Three had percutaneous rib biopsies, two of which came back with benign histology and one was indeterminate. The indeterminate biopsy patient had a RP and his postoperative PSA level was <0.1 µg/L. A total of 43 (69.4%) men with benign rib lesions had a SUVmax greater than the SUVmax of the malignant lesion. CONCLUSION: To our knowledge, this is the first cohort study of men with PSMA-avid solitary rib lesions on pre-treatment 68 Ga-PSMA PET/CT staging scans for prostate cancer. Our results indicate that the vast majority of these lesions have low-intensity uptake and are benign. Intervention to confirm this is not usually required.

Use of a trizonal schema to assess targeting accuracy in prostatic fusion biopsy.

OBJECTIVES: To describe the use of a novel 'trizonal' biopsy schema in which 'near-target' biopsies are taken adjacent to the MRI lesion, in addition to target and systematic biopsies, to determine the accuracy of prostate MRI fusion systems. PARTICIPANTS AND METHODS: A trizonal biopsy technique was used to evaluate 75 men with small Prostate Imaging Reporting and Data System (PI-RADS) 3-5 MRI lesions (<15 mm) identified from a prospective cohort of 290 men undergoing multiparametric magnetic resonance imaging (MRI) for suspected prostate cancer at a single high-volume institution between September 2017 and May 2019. In addition to target and systematic biopsies, near-target biopsies were taken 4 mm from the apparent border of the MRI lesion. Comparisons were made between highest International Society of Urological Pathology grade and longest tumour length. RESULTS: Fifty-three men with significant prostate cancer in the same quadrant as the target were included in the final analysis. The percentages of positive cores from target, near-target and MRI-negative zones were 66%, 39% and 17%, respectively. Significant cancer was detected in the near-target zone in 77% of cases when the target zone was positive. A total of 17% of participants were upgraded by a median (range) of 1 (1-3) grades through the addition of near-target cores. Notably, 9% of men were diagnosed with clinically significant prostate cancer solely via the near-target biopsy cores when the target cores were negative. CONCLUSION: The use of near-target biopsies as part of a trizonal biopsy schema provides a novel methodology to optimize clinically significant prostate cancer detection.

A Virtual Multidisciplinary Care Program for Management of Advanced Chronic Kidney Disease: Matched Cohort Study.

BACKGROUND: It is not well established whether a virtual multidisciplinary care program for persons with advanced chronic kidney disease (CKD) can improve their knowledge about their disease, increase their interest in home dialysis therapies, and result in more planned outpatient (versus inpatient) dialysis starts. OBJECTIVE: We aimed to evaluate the feasibility and preliminary associations of program participation with disease knowledge, home dialysis modality preference, and outpatient dialysis initiation among persons with advanced CKD in a community-based nephrology practice. METHODS: In a matched prospective cohort, we enrolled adults aged 18 to 85 years with at least two estimated glomerular filtration rates (eGFRs) of less than 30 mL/min/1.73 m2 into the Cricket Health program and compared them with controls receiving care at the same clinic, matched on age, gender, eGFR, and presence of heart failure and diabetes. The intervention included online education materials, a virtual multidisciplinary team (nurse, pharmacist, social worker, dietician), and patient mentors. Prespecified follow-up time was nine months with extended follow-up to allow adequate time to determine the dialysis start setting. CKD knowledge and dialysis modality choice were evaluated in a pre-post survey among intervention participants. RESULTS: Thirty-seven participants were matched to 61 controls by age (mean 67.2, SD 10.4 versus mean 68.8, SD 9.5), prevalence of diabetes (54%, 20/37 versus 57%, 35/61), congestive heart failure (22%, 8/37 versus 25%, 15/61), and baseline eGFR (mean 19, SD 6 versus mean 21, SD 5 mL/min/1.73 m2), respectively. At nine-month follow-up, five patients in each group started dialysis (P=.62). Among program participants, 80% (4/5) started dialysis as an outpatient compared with 20% (1/5) of controls (OR 6.28, 95% CI 0.69-57.22). In extended follow-up (median 15.7, range 11.7 to 18.1 months), 19 of 98 patients started dialysis; 80% (8/10) of the intervention group patients started dialysis in the outpatient setting versus 22% (2/9) of control patients (hazard ratio 6.89, 95% CI 1.46-32.66). Compared to before participation, patients who completed the program had higher disease knowledge levels (mean 52%, SD 29% versus mean 94%, SD 14% of questions correct on knowledge-based survey, P<.001) and were more likely to choose a home modality as their first dialysis choice (36%, 7/22 versus 68%, 15/22, P=.047) after program completion. CONCLUSIONS: The Cricket Health program can improve patient knowledge about CKD and increase interest in home dialysis modalities, and may increase the proportion of dialysis starts in the outpatient setting.

Rapid assessment of the latent hazard posed by dissolved mercaptans within aqueous effluent.

The presence of mercaptans (RSH) can usually be detected by their inherent noxious odour but there is a need to quantify the concentration within effluent and hence allow an assessment of the latent hazard to be made prior to disposal. The versatility of using naphthoquinone as a rapid derivatising agent through which to trap such species has been evaluated. The quinone moiety provides a label that can be quantified using colorimetric, electrochemical and chromatographic means and offers a significant advantage over conventional thiol labelling agents. The analytical characteristics of each approach have been investigated and the selectivity, sensitivity and applicability of the reaction system critically assessed for a range of model compounds. The naphthoquinone system has a detection limit in the low micromolar range with little interference from other components common to discharge water with 96% recovery of mercaptopropionate. The reaction to sulfide (HS-) has also been assessed and a disparity in response between the detection methods observed and a possible reaction pathway outlined.

A chromatographic tool for preparing combinatorial quinone-thiol conjugate libraries.

Quinones are well established as key players in the production of reactive oxygen species within cellular environments. Many factors govern their cytotoxicity but most studies have been restricted to a few, core, derivatives. A new strategy for the in situ production of quinone derivatives has been developed such that libraries of diverse functionality can be rapidly created without recourse to extensive synthetic procedures. The approach relies upon nucleophilic addition by reduced thiol derivatives to the quinone core within a pre-culture assay mixture and provides a generic strategy that exploits the large reservoir of commercial thiols currently available. A readily accessible chromatographic method has been developed that allows the derivatisation process to be easily monitored and the purity of the resulting one pot preparation to be assessed. The viability of the combinatorial approach has been fully validated through comparison with a range of quinone-S-conjugates prepared using conventional bench synthesis. The latter have been fully characterised.