Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

BACKGROUND: Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (177Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. FINDINGS: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225Ac-PSMA RLT. All patients who received more than seven cycles of 225Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. INTERPRETATION: 225Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. FUNDING: None.

Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management: Current Practice and Future Perspectives.

Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Timely decision-making that enables implementation of the most appropriate therapy or therapies is essential for achieving the best clinical outcomes in breast cancer. While clinicopathologic characteristics and immunohistochemistry have traditionally been used in decision-making, these clinical and laboratory parameters may be difficult to ascertain or be equivocal due to tumor heterogeneity. Tumor heterogeneity is described as a phenomenon characterized by spatial or temporal phenotypic variations in tumor characteristics. Spatial variations occur within tumor lesions or between lesions at a single time point while temporal variations are seen as tumor lesions evolve with time. Due to limitations associated with immunohistochemistry (which requires invasive biopsies), whole-body molecular imaging tools such as standard-of-care [18F]FDG and [18F]FES PET/CT are indispensable in addressing this conundrum. Despite their proven utility, these standard-of-care imaging methods are often unable to image a myriad of other molecular pathways associated with breast cancer. This has stimulated interest in the development of novel radiopharmaceuticals targeting other molecular pathways and processes. In this review, we discuss validated and potential roles of these standard-of-care and novel molecular approaches. These approaches' relationships with patient clinicopathologic and immunohistochemical characteristics as well as their influence on patient management will be discussed in greater detail. This paper will also introduce and discuss the potential utility of novel PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers of PARP expression/upregulation.

Tachykinin Receptor-Selectivity of the Potential Glioblastoma-Targeted Therapy, DOTA-[Thi8,Met(O2)11]-Substance P.

Radiopharmaceutical development hinges on the affinity and selectivity of the biological component for the intended target. An analogue of the neuropeptide Substance P (SP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8,Met(O2)11]-SP (DOTA-[Thi8,Met(O2)11]SP), in the theranostic pair [68Ga]Ga-/ [213Bi]Bi-DOTA-[Thi8,Met(O2)11]SP has shown promising clinical results in the treatment of inoperable glioblastoma. As the theranostic targeting component, modifications to SP that affect the selectivity of the resulting analogue for the intended target (neurokinin-1 receptor [NK1R]) could be detrimental to its therapeutic potential. In addition to other closely related tachykinin receptors (neurokinin-2 receptor [NK2R] and neurokinin-3 receptor [NK3R]), SP can activate a mast cell expressed receptor Mas-related G protein-coupled receptor subtype 2 (MRGPRX2), which has been implicated in allergic-type reactions. Therefore, activation of these receptors by SP analogues has severe implications for their therapeutic potential. Here, the receptor selectivity of DOTA-[Thi8,Met(O2)11]SP was examined using inositol phosphate accumulation assay in HEK293-T cells expressing NK1R, NK2R, NK3R or MRGPRX2. DOTA-[Thi8,Met(O2)11]SP had similar efficacy and potency as native SP at NK1R, but displayed greater NK1R selectivity. DOTA-[Thi8,Met(O2)11]SP was unable to elicit significant activation of the other tachykinin receptors nor MRGPRX2 at high concentrations nor did it display antagonistic behaviour at these receptors. DOTA-[Thi8,Met(O2)11]SP, therefore has high potency and selectivity for NK1R, supporting its potential for targeted theranostic use in glioblastoma multiforme and other conditions characterised by NK1R overexpression.

Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer.

PURPOSE: Actinium-225-labeled prostate-specific membrane antigen ([225Ac]Ac-PSMA-617) is safe and effective in the treatment of metastatic castration-resistant prostate cancer (mCRPC). No study has specifically assessed its safety in patients with extensive skeletal metastases of mCRPC. We aimed to investigate the hematologic toxicity and efficacy of [225Ac]Ac-PSMA-617 therapy in patients with extensive skeletal metastases of mCRPC. METHODS: We retrospectively reviewed the medical record of patients treated with [225Ac]Ac-PSMA-617 for mCRPC. We included patients with a superscan pattern of skeletal metastases and those with 20 or more multifocal sites of skeletal metastases on baseline [68 Ga]Ga-PSMA-11 PET/CT. We reviewed the levels of hemoglobin, white blood cell (WBC), and platelet prior to each cycle of treatment and determined the presence of impaired bone marrow function at baseline and the grade of toxicity in the hematologic parameters induced by treatment. We evaluated the predictors of hematologic toxicity using binary logistic regression analysis. We also determined the presence of renal dysfunction before or during treatment. We assessed response to treatment using prostate-specific antigen response and the progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 106 patients were included. Skeletal metastasis was in the superscan pattern in 34 patients (32.1%) and multifocal in 72 patients (67.9%). The median treatment cycle was 4 (range = 1-9). Ninety-eight patients (92.5%) had abnormal baseline hematologic parameters. One patient had grade 4 thrombocytopenia. Grade 3 anemia, leukopenia, and thrombocytopenia were seen in 1 (0.9%), 3 (2.8%), and 2 (1.9%) patients, respectively. Age, the number of treatment cycles, and the presence of renal dysfunction were significant predictors of hematologic toxicity. Eighty-five patients (80.2%) achieved PSA response. The median PFS and OS of the study population were 14:00 (95%CI: 8.15-19.86) months and 15.0 (95%CI: 12.8-17.2) months, respectively. CONCLUSIONS: [225Ac]Ac-PSMA-617 induces a good anti-tumor effect in about 80% of patients with extensive skeletal metastases of mCRPC with a rare incidence of severe hematologic toxicity. Age, number of treatment cycles, and the presence of renal dysfunction were significant risk factors for hematologic toxicity of [225Ac]Ac-PSMA-617 therapy.

18F-FDG-PET/CT imaging of uterine cervical cancer recurrence in women with and without HIV infection.

BACKGROUND: To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT. METHODS: We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study. RESULTS: We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (P=0.849). HIV infected patients were younger (41.99±9.30 years) compared to HIV-uninfected (50.19±11.09), P<0.001. Local recurrence was present in 125 patients while 100 patients had a distant recurrence. Recurrence occurred at a single site in 88 patients and two or more sites in 110 patients. No significant difference in the recurrent patterns between HIV-infected and uninfected patients. Median time to recurrence was 10.50 months (range: 6.00-156.00) among HIV-infected versus 12.00 months (IQR:7.00-312.00) among the uninfected, P=0.065. FIGO stage III (P=0.042) and the presence of histological sub-types other than SCC (P=0.005) were significant predictors of recurrence. HIV infection by itself was not significant in predicting recurrence (P=0.843). CONCLUSIONS: HIV infection has no significant impact on the rate, time or pattern of recurrence in women with suspected cervical carcinoma recurrence. Advanced disease and histological variant other than SCC are predictive of recurrence.

Cardiovascular disturbances in COVID-19: an updated review of the pathophysiology and clinical evidence of cardiovascular damage induced by SARS-CoV-2.

Severe acute respiratory coronavirus-2 (SARS-Co-2) is the causative agent of coronavirus disease-2019 (COVID-19). COVID-19 is a disease with highly variable phenotypes, being asymptomatic in most patients. In symptomatic patients, disease manifestation is variable, ranging from mild disease to severe and critical illness requiring treatment in the intensive care unit. The presence of underlying cardiovascular morbidities was identified early in the evolution of the disease to be a critical determinant of the severe disease phenotype. SARS-CoV-2, though a primarily respiratory virus, also causes severe damage to the cardiovascular system, contributing significantly to morbidity and mortality seen in COVID-19. Evidence on the impact of cardiovascular disorders in disease manifestation and outcome of treatment is rapidly emerging. The cardiovascular system expresses the angiotensin-converting enzyme-2, the receptor used by SARS-CoV-2 for binding, making it vulnerable to infection by the virus. Systemic perturbations including the so-called cytokine storm also impact on the normal functioning of the cardiovascular system. Imaging plays a prominent role not only in the detection of cardiovascular damage induced by SARS-CoV-2 infection but in the follow-up of patients' clinical progress while on treatment and in identifying long-term sequelae of the disease.

Immune reconstitution inflammatory syndrome-associated Graves disease in HIV-infected patients: clinical characteristics and response to radioactive iodine therapy.

OBJECTIVES: We aimed to describe the clinical characteristics and the response to radioactive iodine (RAI) treatment of immune reconstitution inflammatory syndrome-associated Graves disease (IRIS-GD) in comparison to Graves disease (GD) seen in HIV-uninfected patients. METHODS: We retrospectively reviewed the medical records of patients treated with RAI for GD. We obtained clinical, biochemical and HIV-related information of patients from their medical records. We compared patient characteristics and response to RAI treatment between patients with IRIS-GD and GD seen in HIV-uninfected patients. RESULTS: A total of 253 GD patients, including 51 patients with IRIS-GD, were included. Among IRIS-GD patients, CD4 cell nadir was 66 cells/µL (range: 37-103) with a peak HIV viral load of 60 900 copies/mL (range: 36 542-64 500). At the time of diagnosis of IRIS-GD, all patients had a completely suppressed HIV viraemia with a CD4 cell count of 729 cells/µL (range: 350-1279). The median interval between the commencement of HIV treatment and the onset of GD was 63 months. At 3 months follow-up, the proportion of patients with IRIS-GD achieving a successful RAI treatment outcome (euthyroid/hypothyroid state) was lower than that of HIV-uninfected patients (35.3% vs. 63.4%, respectively; p < 0.001). The response rate remained lower (60.8%) among patients with IRIS GD than among HIV-uninfected GD patients (80.2%, p = 0.004) at 6 months follow-up. After correcting for differences in age, gender and pre-treatment thyroid-stimulating hormone level, there was no significant difference in RAI treatment response between the two groups. CONCLUSIONS: After correcting for possible confounders, the response to RAI treatment was not different between patients with IRIS-GD and GD in HIV-uninfected patients.

Global experience with PSMA-based alpha therapy in prostate cancer.

PURPOSE: This review discusses the current state of prostate-specific membrane antigen (PSMA)-based alpha therapy of metastatic castration-resistant prostate cancer (mCRPC). With this in-depth discussion on the growing field of PSMA-based alpha therapy (PAT), we aimed to increase the interactions between basic scientists and physician-scientists in order to advance the field. METHODS: To achieve this, we discuss the potential, current status, and opportunities for alpha therapy and strategies, attempted to date, and important questions that need to be addressed. The paper reviews important concepts, including whom to treat, how to treat, what to expect regarding treatment outcome, and toxicity, and areas requiring further investigations. RESULTS: There is much excitement about the potential of this field. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other conventional therapies. CONCLUSION: A better understanding of the strengths and limitations of PAT may help in creating an effective therapy for mCRPC and design a rational combinatorial approach to treatment by targeting different tumor pathways.

A prospective intra-individual comparison of [68Ga]Ga-PSMA-11 PET/CT, [68Ga]Ga-NODAGAZOL PET/CT, and [99mTc]Tc-MDP bone scintigraphy for radionuclide imaging of prostate cancer skeletal metastases.

PURPOSE: Prostate cancer (PCa) commonly metastasizes to the bones. There are several radionuclide techniques for imaging PCa skeletal metastases. We aimed to compare the lesion detection rate of [68Ga]Ga-PSMA-11 PET/CT, [68Ga]Ga-NODAGA-zoledronate ([68Ga]Ga-NODAGAZOL) PET/CT, and [99mTc]Tc-MDP bone scan in the assessment of bone metastases in patients with advanced PCa. METHODS: We prospectively recruited two cohorts of patients (staging and re-staging cohorts) with advanced prostate cancer. The staging cohort was treatment-naïve PCa patients who showed skeletal metastases on bone scan. These patients were subsequently imaged with [68Ga]Ga-PSMA-11 PET/CT and [68Ga]Ga-NODAGAZOL PET/CT. Re-staging cohort was patients who were previously treated with PSMA-based radioligand therapy and were experiencing PSA progression. The re-staging cohort was imaged with [68Ga]Ga-PSMA-11 PET/CT and [68Ga]Ga-NODAGAZOL PET/CT. We performed a per-patient and per-lesion analysis of skeletal metastases in both cohorts and made a comparison between scan findings. RESULTS: Eighteen patients were included with a median age of 68 years (range = 48-80) and a median Gleason score of 8. There were ten patients in the staging cohort with a median PSA of 119.26 ng/mL (range = 4.63-18,948.00) and eight patients in the re-staging cohort with a median PSA of 48.56 ng/mL (range = 6.51-3175.00). In the staging cohort, skeletal metastases detected by [68Ga]Ga-PSMA-11 PET/CT, [68Ga]Ga-NODAGAZOL PET/CT, and bone scan were 322, 288, and 261, respectively, p = 0.578. In the re-staging cohort, [68Ga]Ga-PSMA-11 PET/CT and [68Ga]Ga-NODAGAZOL PET/CT detected 152 and 191 skeletal metastases, respectively, p = 0.529. In two patients with negative [68Ga]Ga-PSMA-11 PET/CT findings, [68Ga]Ga-NODAGAZOL detected one skeletal metastasis in one patient and 12 skeletal metastases in the other. CONCLUSION: In patients with advanced prostate cancer, [68Ga]Ga-PSMA-11 PET/CT may detect more lesions than [68Ga]Ga-NODAGAZOL PET/CT and [99mTc]Tc-MDP bone scan for the staging of skeletal metastases. In patients who experience PSA progression on PSMA-based radioligand therapy, [68Ga]Ga-NODAGA PET/CT is a more suitable imaging modality for the detection of skeletal lesions not expressing PSMA. In the setting of re-staging, [68Ga]Ga-NODAGAZOL PET/CT may detect more lesions than [68Ga]Ga-PSMA-11 PET/CT.

Comparison of MRI, [18F]FDG PET/CT, and 99mTc-UBI 29-41 scintigraphy for postoperative spondylodiscitis-a prospective multicenter study.

PURPOSE: Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. METHODS: Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). RESULTS: Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64-0.92) and 0.80 (95% CI: 0.64-0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80-1.00). CONCLUSION: [18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.

Impact of optimized PET imaging conditions on 18F-FDG uptake quantification in patients with apparently normal aortas.

BACKGROUND: The cardiovascular committee of the European Association of Nuclear Medicine (EANM) recently published recommendations on imaging conditions to be observed during 18F-FDG PET imaging of vascular inflammation. This study aimed to evaluate the impact of applying these optimized imaging conditions on PET quantification of arterial 18F-FDG uptake. METHODS AND RESULTS: Fifty-seven patients were prospectively recruited to undergo an early 18F-FDG PET/CT imaging at 60 minutes and repeat delayed imaging at ≥ 120 minutes post tracer injection. Routine oncologic 18F-FDG PET protocol was observed for early imaging, while delayed imaging parameters were optimized for vascular inflammation imaging as recommended by the EANM. Aortic SUVmax of the ascending aorta and SUVmean from the lumen of the superior vena cava (SVC SUVmean) were obtained on early and delayed imaging. Target-to-background ratio (TBR) was obtained for the early and delayed imaging. Aortic SUVmax increased by a mean of 70%, while SVC SUVmean decreased by a mean of 52% between early and delayed imaging (P < 0.001). TBR increased by 122% following delayed imaging. TBR increased, while SVC SUVmean declined across all time-points from 120 to > 180 minutes. Aortic SUVmax significantly increased at imaging time-points between 120 and 180 minutes. No significant improvement in aortic SUVmax was seen at imaging time-points beyond 180 minutes. CONCLUSIONS: 18F-FDG PET imaging conditions optimized for vascular inflammation imaging lead to an improved quantification through an increase in the quantified vascular tracer uptake and decrease in blood-pool background activity.

Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach.

Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.

Radionuclide imaging of hypoxia: Where are we now? Special attention to cancer of the cervix uteri.

Cancer of the cervix is the fourth commonest malignancy in women worldwide and it also ranks fourth as the cause of cancer related mortality in women. Hypoxia is a common characteristic of solid tumours and cervical cancer is no exception. Hypoxia is associated with increased aggressiveness, risk of invasion and metastasis. Tumour hypoxia also results in resistance to both radiation therapy and chemotherapy leading to a poorer prognosis. In-vivo measurement of tumour hypoxia is vital in oncologic practice because it can predict outcome and identify patients with a worse prognosis. Mapping of tumour hypoxia may also help select patients that may benefit from applicable treatments. While traditional methods of measuring hypoxia such as the Eppendorf probe is considered the gold standard, it is invasive and technically demanding. Non-invasive methods of measuring tumourhypoxia are ideal. Positron emission tomography/computed tomography (PET/CT) imaging with nitro-imidazole-based tracers is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of hypoxia. Over the years various hypoxia specific PET tracers have been investigated in various malignancies including cancer of the cervix. Several fluorine-18 (18F)-based tracers have been studied and although most had small patient numbers, the results are promising and generally demonstrate an associate between the presence of hypoxia and treatment outcome. The need for an onsite cyclotron and specialized radiopharmacy skills make these tracers unattractive and largely unavailable for routine clinical applications. With the increase in availability of the gallium-68 (68Ga) generator this makes the 68Ga-labelled nitroimidazole derivatives attractive because 68Ga is available from a generator with a shelf life of almost a year. The chemistry of 68Ga makes for easy labelling with several peptides and molecules. Pre-clinical work has demonstrated the feasibility of using these tracers for imaging hypoxia and has laid the groundwork for further human studies with these tracers.The aim of this review is to discuss hypoxia and its impact in cancer of the cervix as well as to look into the progress made in hypoxia imaging in cancer of the cervix. This will focus on the tracers studied thus far and some of the challenges of hypoxia imaging.

A comparison of the diagnostic performance of 18F-PSMA-1007 and 68GA-PSMA-11 in the same patients presenting with early biochemical recurrence.

OBJECTIVE: Accurate early assessment of biochemical recurrence is essential in determining the correct treatment plan for patients with prostate cancer. Gallium-68-prostate-specific membrane antigen-11 (68Ga-PSMA-11) targeting PSMA has been at the forefront of imaging in biochemical recurrence however the emergence of fluorine-18 (18F)-PSMA-1007 may prove to be advantageous over the 68Ga-PSMA-11 molecule due to its physical and physiologic al attributes. The aim of our study was to assess the diagnostic performance of 18F-PSMA-1007 as compared to that of 68Ga-PSMA-11 in the same patients who presented with biochemical recurrence. MATERIAL AND METHODS: Twenty-one patients with biochemical recurrence prostate cancer were prospectively enrolled into the study. Fluorine-18-PSMA-1007 positron emission tomography/computed tomography (PET/CT) was performed on the same patient after 68Ga-PSMA-11 PET/CT had been performed. Recurrence diagnosed on each of these studies was compared against a final diagnosis based on clinical follow-up and histological correlation where available. RESULTS: Gallium-68-PSMA-11 identified fifteen (71,4%) patients as being negative for recurrence whilst five (23.8%) were identified as positive and one (4.8%) as uncertain. In comparison 18F-PSMA-1007 identified eight (38.1%) as being positive with thirteen (61.9%) patients' scans identified as negative for recurrence. No scans were classified as uncertain for the 18F-PSMA-1007 group. Fluorine-18-PSMA-1007 identified 8 lesions as positive for disease recurrence whilst only 6 lesions were identified on 68Ga-PSMA-11. Of the 8 patients identified as having recurrence on 18F-PSMA-1007 4 of those demonstrated local prostatic recurrence. The rest demonstrated local nodal recurrence and skeletal metastases. Fluorine-18-PSMA-1007 demonstrated a sensitivity, specificity, positive and negative predictive value of 88.9%, 100%, 100%, and 92.3% respectively whilst 68Ga-PSMA-11 demonstrated a sensitivity, specificity, positive and negative predictive value of 44.4%, 83.3%, 80%, and 66.6%, respectively. CONCLUSION: In our pilot study 18F-PSMA-1007 was able to detect more sites of recurrence as compared to 68Ga-PSMA-11 which were mainly within the prostate and surrounding pelvic structures.

Prostate-specific membrane antigen-targeted endoradiotherapy in metastatic prostate cancer.

PURPOSE OF REVIEW: In this review, we present an update on the safety and efficacy of prostate-specific membrane antigen (PSMA) radioligand therapy (PRLT) of metastatic castration-resistant prostate cancer (mCRPC). RECENT FINDINGS: Treatment of mCRPC with approved treatment agents leads to a survival advantage. The disease often progresses despite these treatments. PRLT with Lutetium-177 and Actinium-225 labeled with PSMA (LuPSMA and AcPSMA) have recently been shown to be effective and well tolerated for mCRPC treatment. LuPSMA is currently applied in patients who have exhausted approved treatment options or in whom these approved treatments are contraindicated. In this category of heavily pretreated patients, prostate-specific antigen (PSA) response (≥50% decline) is achieved in about 46% of patients. Side-effects are tolerable with rare reports of grade III-IV treatment-induced toxicity. AcPSMA is currently applied on a smaller scale in patients who relapsed after LuPSMA or in whom LuPSMA is contraindicated. PSA response occurs in up to 88% of patients treated with AcPSMA. SUMMARY: PRLT with LuPSMA and AcPSMA is a well-tolerated and effective treatment modality for mCRPC. Prospective randomized control trials are necessary to facilitate its application as an approved therapy option.

Role of FDG PET/CT in monitoring treatment response in patients with invasive fungal infections.

INTRODUCTION: Invasive fungal infections (IFIs) occur mostly in immunosuppressed patients and can be life-threatening. Inadequate treatment is associated with high morbidity and mortality. We examined the role of 2-fluorodeoxyglucose positron emission tomography integrated with CT (FDG-PET/CT) in monitoring IFIs and therapy decision-making, and evaluated the role of baseline metabolic parameters in predicting the metabolic response. METHODS: All patients between October 2009 and March 2018, diagnosed with IFIs, treated with antifungal drugs, and who underwent FDG-PET/CT at baseline and at one or more timepoints during treatment were retrospectively included. The electronic patient files were reviewed for pathology, microbiology, and laboratory findings. All FDG-PET/CT scans were performed according to standardized European Association of Nuclear Medicine/EANM Research Limited (EANM/EARL) protocols. For each scan, the global total lesion glycolysis (TLG) and metabolic volume (MV), highest maximum standardized uptake value (SUVmax), and peak standardized uptake value (SUVpeak) were determined. The role of FDG-PET/CT on monitoring antifungal therapy was assessed by looking at the clinical decision made as result of the scan. Furthermore, the added value of the baseline metabolic parameters in predicting metabolic response to the antifungal treatment was evaluated. RESULTS: Twenty-eight patients with in total 98 FDG-PET/CT scans were included with a mean age of 43 ± 22 years. FDG-PET/CT altered management in 14 out of the 28 patients (50%). At the final FDG-PET/CT scan, 19 (68%) had a complete metabolic response (CMR), seven a partial response and two patients were defined as having progressive disease. Using receiver operative analysis, the cut-off value, sensitivity, specificity, and significance for the baseline TLG and MV to discriminate patients with CMR were 160, 94%, 100%, p < 0.001 and 60, 84%, 75%, p = 0.001 respectively. CONCLUSION: FDG-PET/CT is useful in the monitoring of IFIs resulting in management therapy change in half of the patients. Baseline TLG and MV were found to be able to predict the metabolic response to antifungal treatment.

Arterial inflammation in young patients with human immunodeficiency virus infection: A cross-sectional study using F-18 FDG PET/CT.

BACKGROUND: HIV infection is associated with the risk of development of atherosclerosis at a younger age. We compared arterial inflammation in HIV-infected and HIV-uninfected patients with otherwise low-risk factors for cardiovascular disease (CVD) using FDG PET/CT. METHODS: 242 patients aged 18-40 years with low-risk factors for CVD consisting of 121 HIV-infected patients and 121 HIV-uninfected age- and gender-matched controls were studied, mean age = 34.95 ± 5.46 years. We calculated and compared the target-to-background ratio of FDG uptake in ascending aorta of HIV-infected and non-infected patients. RESULTS: Median CD4 count and viral load were 375.5 cells/mm3 (range 2-1094) and 6391.00 copies/mL (range 24-1,348,622), respectively. There was slightly higher but significant overlap in the TBR between HIV-infected group compared with control (1.22, 0.87-2.02 vs. 1.12, 0.38-1.40, P < 0.001). TBR was neither affected by CD4 count levels nor the presence or absence of detectable viremia. We also found no significant difference in TBR between male and female patients with HIV infection. We found a weak positive correlation between TBR and CD4 count, TBR and duration of HIV infection, and a very weak negative correlation between TBR and viral load. There was no significant difference in TBR between patients on HAART and those not yet commenced on therapy. CONCLUSION: Marginally higher TBR with a significant overlap exist in HIV-infected patients compared with control. Arterial F-18 FDG uptake is not affected by the CD 4 count, viral load, gender, or duration of HIV infection.

Diagnostic utility of 18F-FDG PET/CT in fever of unknown origin among patients with end-stage renal disease treated with renal replacement therapy.

OBJECTIVE: To evaluate the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in identifying the cause of fever of unknown origin (FUO) in patients on renal replacement therapy (RRT) for end-stage renal disease (ESRD). SUBJECTS AND METHODS: We retrospectively reviewed the 18F-FDG PET/CT scans of 46 patients with a mean age of 39.28±12.50 years on RRT for ESRD. All patients with abnormal scans had histopathologic examination and microbial cultures of tissue samples from areas with increased standardized uptake value maximum (SUVmax) suggesting the cause of FUO in the 18F-FDG PET/CT scan. Fluorine-18-FDG PET/CT was considered helpful if it led to the diagnosis of the cause of FUO after histopathologic and microbiologic examinations. RESULTS: Fluorine-18-FDG PET/CT was helpful in identifying the cause of FUO in 22/46 patients (47.83%). Infection was the cause of fever in all these 22 patients. C-reactive protein (CRP) (P=0.003) and procalcitonin levels (P=0.021) were higher in patients with helpful 18F-FDG PET/CT. No significant difference was found in blood sugar levels and leucocytes counts between patients with helpful 18F-FDG PET/CT outcome and those without. By multiple regression analysis, the odds of a helpful 18F-FDG PET/CT increased with every unit increase in CRP level (OR: 1.009; 95% CI: 1.003-1.016; P=0.005). CONCLUSION: About half of the 18F-FDG-PET/CT scans (22/46) identified the cause of FUO in patients on RRT for ESRD. The clinical utility of 18F-FDG PET/CT in this group of patients is comparable to its average performance in the unselected patients' population evaluated for FUO. A higher CRP level was predictive of a positive 18F-FDG PET/CT outcome.

Use of a Sentinel Lymph Node Biopsy Algorithm in a South African Population of Patients With Cervical Cancer and High Prevalence of Human Immunodeficiency Virus Infection.

OBJECTIVES: Cervical cancer is common in resource-poor settings with high prevalence of tuberculosis, pelvic inflammatory disease, and human immunodeficiency virus (HIV) infection. There are no data regarding the sentinel lymph node (SLN) algorithm in these high-risk cancer populations. Our objectives were to establish the sensitivity, specificity, positive predictive value, and negative predictive value of the SLN algorithm in cervical cancer and to compare the detection rate of indocyanine green (ICG) versus blue dye versus technetium Tc 99m nanocolloid (Tc). METHODS: This prospective study was conducted at the University of Pretoria. Tc-nanocolloid tracer, ICG dye, and methylene blue (MB) were used to detect SLNs. Pathological ultrastaging was performed on hematoxylin-eosin- negative nodes. RESULTS: Results of 72 women were analyzed. The mean age was 47.2 years, 5.5% had a history of tuberculosis, 18.1% had pelvic inflammatory disease, and 65.3% were HIV positive. The SLN detection rate was 65.3%. Detection rate of MB was 56.9%; Tc, 69.4%; ICG, 87.5%; and the combination of MB and Tc, 91.7%. Pelvic nodal metastases occurred in 26.4%. The sensitivity, specificity, negative predictive value, and positive predictive value of SLN biopsy were 85.7%, 100%, 100%, and 98.33%, respectively. The false-negative rate was 14.3%, and it was 0% if the algorithm was applied. CONCLUSIONS: The SLN algorithm is a feasible option for use in cervical cancer women with a high prevalence of HIV infection. The detection rate is generally lower, but in select subgroups of women, it was comparable to that reported elsewhere. This is the first report of the use of SLN biopsy in a substantial group of HIV-infected women.

Cryptococcoma of a transplanted kidney in a patient presenting with recurrent urinary tract infection: a case report.

BACKGROUND: Cryptococcosis is an important opportunistic infection of organ transplant recipients. It is the third most common fungal infection of transplant patients and occurs especially in kidney recipients. Cryptococcus neoformans is a ubiquitous fungus which infects humans by inhalation of spores. C. gattii has more recently been recognised as a pathogen. Infection commonly is disseminated affecting mainly the central nervous system and the lungs. Cryptococcoma, a localised form of the disease, has been described in various organs. We present a unique case of a cryptococcoma in a transplanted kidney. The lesion was not seen on ultrasound or uncontrasted computerised tomography but was detected by FDG-PET/CT. CASE PRESENTATION: A 30 year old woman received a deceased donor kidney transplant in 2005. Due to chronic allograft nephropathy in 2014, cyclosporine and azathioprine immunosuppression was changed to tacrolimus and mycophenolate. After rapid deterioration of renal function in 2015 due to suspected non-adherence to immunosuppressants, steroid pulses were administered. The patient developed severe recurrent bacterial urinary tract infections and demonstrated several features of severe immunosuppression. She was treated for cytomegalovirus infection and BK virus was demonstrated in the urine. In addition, Kaposi sarcoma of the stomach was diagnosed on endoscopic biopsy. A metabolically-active lesion of the kidney transplant was imaged on FDG-PET/CT scan. Biopsy of the lesion demonstrated infection with cryptococcus. Escherichia coli with the same antibiotic sensitivity spectrum as that in the urine was cultured from the biopsy. Cryptococcus was not cultured from urine at that time or from several subsequent specimens. The lesion was not detected by conventional imaging. The patient manifested no other evidence of cryptococcosis. The lesion responded poorly to treatment with fluconazole. CONCLUSIONS: This is probably the first report of a case of a cryptococcoma in a transplanted organ. FDG-PET/CT scan, which is dependent on cellular metabolism, proved useful in visualising the lesion. Clinicians should be aware of this rare presentation of cryptococcosis in organ transplant recipients.