A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours.Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia.We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours.Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.
A new era of precision diagnostics and therapy for patients with neuroendocrine neoplasms began with the approval of somatostatin receptor (SSTR) radiopharmaceuticals for PET imaging followed by peptide receptor radionuclide therapy (PRRT). With the transition from SSTR-based γ-scintigraphy to PET, the higher sensitivity of the latter raised questions regarding the direct application of the planar scintigraphy–based Krenning score for PRRT eligibility. Also, to date, the role of SSTR PET in response assessment and predicting outcome remains under evaluation. In this comprehensive review article, we discuss the current role of SSTR PET in all aspects of neuroendocrine neoplasms, including its relation to conventional imaging, selection of patients for PRRT, and the current understanding of SSTR PET–based response assessment. We also provide a standardized reporting template for SSTR PET with a brief discussion.
The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer. 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 patients with biochemically recurrent prostate cancer. Each subject served as his own control. PET/CT imaging sessions using 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were performed 3–7 d apart, after oral administration of either 12.7 g of MSG or placebo. Data from the 2 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 region-of-interest data. Results: In total, 142 pathologic lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in SUVmax corrected for lean body mass (SULmax) on images obtained after 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 the 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). A 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 than on the placebo studies (SULmax median decrease, 33%; range, −1% to 75%; P < 0.001). No significant adverse events occurred after placebo or MSG administration, and vital signs were stable. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney, and other normal-organ PSMA radiotracer uptake in human subjects, using 18F-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.
Abstract Background Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming standard of care for men with biochemical recurrence (BCR) of prostate cancer. The implications of a negative PSMA PET/CT scan in this population remain unclear. This study aims to assess the outcome of patients with BCR post radical prostatectomy (RP) who have negative [ 18 F]DCFPyL PET/CT scan at relapse. Methods This is a post-hoc subgroup analysis of a prospective non randomized clinical trial. One hundred and one patients (median age, 75 years) with BCR after RP, who tested negative on [ 18 F]DCFPyL PET/CT and subsequently either underwent salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) or were followed without active treatment, were included. Freedom from progression (FFP) after negative PSMA PET/CT was determined based on follow-up imaging selected as per clinical practice. Uni- and multivariate Cox regression analyses were performed to examine the association of patients' characteristics, tumor-specific variables, and treatment with clinical progression at the last follow-up. FFP at 1-, 2-, and 3-year were reported using Kaplan Meier analysis. Results The median PSA level at PET/CT was 0.56 ng/mL (range, 0.4–11.3). Sixty five (64%) patients were followed without receiving further treatment, and 36 (36%) received sRT (18% to the prostate bed only and 18% to the prostate bed and pelvic lymph nodes) within 3 months of the PSMA PET. Seventeen of the sRT patients (17 of 36, 47%) received concomitant androgen deprivation therapy (ADT). Median follow-up was 39 months. Subsequent clinical progression was detected in 21 patients (21%), with 52% in pelvic lymph nodes, 52% in the prostatic fossa, 19% in distant lymph nodes, 14% in lungs, and 10% in bones. The FFP was 95% (95% CI: 91%-99%) at 12 months, 87% (95% CI: 81%-94%) at 24 months, and 79% (95% CI: 71%-88%) at 36 months. Multivariate Cox regression analysis revealed that an initial International Society of Urological Pathology (ISUP) grade 5 was significantly associated with clinical progression at the last follow-up (hazard ratio, 5.1, P value, 0.04). Furthermore, the receipt of sRT correlated significantly with lower clinical progression at the last follow-up (hazard ratio, 0.2, P value, 0.03), whereas other clinical and tumor-specific parameters did not. Following surveillance-only and sRT, 29% (19 of 65) and 6% (2 of 36) of patients, respectively, showed clinical progression. In the sRT group, no significant difference was observed in FFP between patients who underwent sRT to the prostatic fossa versus those who received sRT to the prostatic fossa and pelvic lymph nodes, although the numbers in these groups were small. Conclusions This study suggests that salvage radiotherapy is associated with a decreased or delayed clinical progression in patients with biochemical recurrence following radical prostatectomy who have negative PSMA PET/CT scan results. The analysis also underscores the prognostic significance of the initial ISUP grade, with ISUP grade 5 being associated with worse outcomes. Trial registration Registered September 14, 2016; NCT02899312 .
Extracted from text ... GUEST EDITORIAL
DON WILSON
Sc, MB ChB, FC Psych
(SA)
Principal
Specialist
and Senior
Lecturer
Department of
sychiatry and Mental
Health
University of Cape
Town and
Groote Schuur
Hospital
on Wilson's interests
are the anxiety disorers,
chemical dependence
and the teaching
of
psychiatry.
SAVILLE
FURMAN
MB ChB, MFGP (SA)
General
Practitioner
Milnerton
Cape Town
r Saville Furman has
een a family physiian
since 1974. He is
a member of the
Western Cape
Academy of Family
ractice/Primary Care
Committee, Part-time
Lecturer in
Community Medicine
at UCT and in
aediatrics, Red Cross
Children's Hospital.
122 C M E Ma rc h ..
A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours. Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.
Introduction: Prostate incidentalomas are prostatic lesions suspicious for cancer discovered by imaging patients without a known history of prostatic cancer (CaP) for other reasons. 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET) is used to diagnose, stage and assess response to treatment for numerous cancers, but it is not routinely used for CaP. We aimed to determine the rate of detection of prostate incidentalomas in patients undergoing FDG PET and to evaluate the natural history of these lesions.
Methods: A retrospective review was conducted of all FDG PET scans performed between 2005 and 2017 at a single institution. Patients were selected who had prostatic uptake without a history of prostate cancer. Clinical data were collected from electronic medical records to determine how the prostate incidentalomas were further evaluated and define the rate of malignancy.
Results: A prostate incidentaloma was identified in 309 (1.0%) of 31 019 FDG PET scans performed on men. A prostate-specific antigen (PSA) test was obtained in 40.1% of patients within six months of prostate incidentaloma detection. Six patients underwent a multiparametric magnetic resonance imaging (MRI) of the prostate, which identified CaP in one case. Overall, CaP was diagnosed in 33 cases, representing 10.7% of the prostate incidentalomas and 0.1% of the scanned patients. CaP was intermediate- or high-risk in 27 (8.7%) of the prostate incidentalomas.
Conclusions: Incidental lesions detected in the prostate by FDG PET may represent clinically significant CaP. Referral to a urologist for further evaluation should be considered if the patient is otherwise in reasonable health.
