The Diagnostic Performance of 18F-PSMA-1007 PET/CT in Prostate Cancer Patients with Early Recurrence after Definitive Therapy with a PSA <10 ng/ml.

AIM: The prostate bed is one of the common sites of early recurrence of prostate cancer. The currently used PSMA ligands (68Ga-PSMA-11 and 99mTc-PSMA) undergo early urinary clearance resulting in interfering physiological activity within and surrounding the prostate. This can result in sites of cancer recurrence being obscured. 18F-PSMA-1007 has an advantage of delayed urinary clearance thus the prostate region is reviewed without any interfering physiological activity. The aim of this study was to determine the diagnostic performance of 18F-PSMA-1007 PET/CT in patients with early biochemical recurrence after definitive therapy. METHODS: Forty-six Prostate cancer (mean age 66.7±7.5, range 48-87 years) presenting with biochemical recurrence (median PSA 1.6ng/ml, range 0.1-10.0) underwent non-contrast-enhanced 18F-PSMA-1007 PET/CT. PET/CT findings were evaluated qualitatively and semiquantitatively (SUVmax) and compared to the results of histology, Gleason grade, and conventional imaging. RESULTS: Twenty-four of the 46 (52.2%) patients demonstrated a site of recurrence on 18F-PSMA-1007 PET/CT. Oligometastatic disease was detected in 15 (32.6%) of these patients. Of these 10 (37.5%) demonstrated intra-prostatic recurrence, lymph node disease was noted in 11 (45.8%) whilst two patients demonstrated skeletal metastases. The detection rates for PSA levels 0-<0.5, 0.5-<1, 1-2, >2 were 31.3%, 33.3%, 55.6% and 72.2% respectively. 7 (29.2%) of the positive patients had been described as negative or equivocal on conventional imaging. An optimal PSA cut-off level of 1.3ng/ml was found. CONCLUSION: 18F-PSMA-1007 demonstrated good diagnostic performance detecting sites of recurrence. Its ability to detect sites of recurrence in the setting of early biochemical recurrence will have a significant impact on patient management.

Diagnostic Performance and Clinical Impact of 68Ga-PSMA-11 PET/CT Imaging in Early Relapsed Prostate Cancer After Radical Therapy: A Prospective Multicenter Study (IAEA-PSMA Study).

Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients, as recurrence localization guides subsequent therapies. The use of PET with prostate-specific membrane antigen (PSMA) provides better accuracy than conventional imaging practice. This prospective, multicenter, international study was performed to evaluate the diagnostic performance and clinical impact of PSMA PET/CT for evaluating BCR in PCa patients in a worldwide scenario. Methods: Patients were recruited from 17 centers in 15 countries. Inclusion criteria were histopathologically proven prostate adenocarcinoma, previous primary treatment, clinically established BCR, and negative conventional imaging (CT plus bone scintigraphy) and MRI results for patients with PSA levels of 4-10 ng/mL. All patients underwent PET/CT scanning with 68Ga-PSMA-11. Images and data were centrally reviewed. Multivariate logistic regression analysis was applied to identify the independent predictors of PSMA-positive results. Variables were selected for this regression model on the basis of significant associations in the univariate analysis and previous clinical knowledge: Gleason score, the PSA level at the time of the PET scan, PSA doubling time, and primary treatment strategy. All patients were monitored for a minimum of 6 mo. Results: From a total of 1,004 patients, 77.7% were treated initially with radical prostatectomy and 22.3% were treated with radiotherapy. Overall, 65.1% had positive PSMA PET/CT results. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment (P < 0.001). Treatment was modified on the basis of PSMA PET/CT results in 56.8% of patients. PSMA PET/CT positivity rates were consistent and not statistically different among countries with different incomes. Conclusion: This multicenter, international, prospective trial of PSMA PET/CT confirmed its capability for detecting local and metastatic recurrence in most PCa patients in the setting of BCR. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment. PSMA PET/CT results led to changes in therapeutic management in more than half of the cohort. The study demonstrated the reliability and worldwide feasibility of PSMA PET/CT in the workup of PCa patients with BCR.

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.

Pattern of Prostate Cancer Recurrence Assessed by 68Ga-PSMA-11 PET/CT in Men Treated with Primary Local Therapy.

Imaging plays a vital role in detecting the recurrence of prostate cancer (PCa) to guide the choice of salvage therapy. Gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) is useful for detecting PCa recurrence. We assessed the pattern of PCa recurrence stratified by serum prostate-specific antigen level and type of primary local treatment in men with biochemical recurrence (BCR) after primary local therapy with radical prostatectomy or external beam radiotherapy (EBRT) using 68Ga-PSMA-11 PET/CT. We reviewed patients imaged with 68Ga-PSMA-11 PET/CT for the localization of the site of PCa recurrence. We determined the site and number of lesions due to PCa recurrence at different PSA levels. A total of 247 men (mean age of 65.72 ± 7.51 years and median PSA of 2.70 ng/mL (IQR = 0.78-5.80)) were included. 68Ga-PSMA-11 PET/CT detected the site of recurrence in 81.4% of patients with a median number of lesions per patient of 1 (range = 1-5). 68Ga-PSMA-11 PET/CT positivity was 43.6%, 75.7%, 83.3%, 90.0%, and 95.8% at PSA levels of <0.5, 0.5-1.0., 1.1-2.0, 2.1-5.0, and 5.0-10.0, respectively. The most common site of recurrence was in the prostate gland/bed at all PSA levels. Pelvic, extra-pelvic, and combined pelvic and extra-pelvic sites of recurrence were seen in 118, 50, and 33 patients, respectively. The risk of extra-pelvic recurrence increases with rising PSA levels. 68Ga-PSMA-11 PET/CT has a high lesion detection rate for biochemical recurrence of PCa in patients previously treated with primary local therapy.

PSMA Theranostics: Science and Practice.

Prostate cancer (PCa) causes significant morbidity and mortality in men globally. While localized PCa may be managed with curative intent by surgery and/or radiation therapy, the management of advanced hormone resistant metastatic disease (mCRPC) is more challenging. Theranostics is a principle based on the ability to use an organ specific ligand and label it to both a diagnostic and a therapeutic agent. The overexpression of prostate specific membrane antigen (PSMA) on prostate cancer cells creates a unique opportunity for development of targeted radionuclide therapy. The use of both beta and alpha emitting particles has shown great success. Several clinical trials have been initiated assessing the efficacy and safety profile of these radionuclide agents. The results are encouraging with PSMA directed radioligand therapy performing well in patients who have exhausted all other standard treatment options. Future studies need to assess the timing of introduction of these radionuclide therapies in the management schema of mCRPC. Drugs or therapies are not without side effects and targeted radionuclide therapies presents a new set of toxicities including xerostomia and myelosuppression. New therapeutic strategies are being explored to improve outcomes while keeping toxicities to a minimum. This review aims to look at the various PSMA labelled tracers that form part of the theragnostic approach and subsequently delve into the progress made in the area of radionuclide therapy.

The Association of Tumor Burden by 18F-FDG PET/CT and Survival in Vulvar Carcinoma.

PURPOSE: The aim of this study was to assess the impact of 18F-FDG PET/CT metabolic parameters obtained at initial staging of vulva carcinoma on survival in women with and without HIV infection. PATIENTS AND METHODS: 18F-FDG PET/CT images of women with vulva cancer who are planned for definitive therapy were analyzed. SUVmax, SUVmean, MTV, and total lesion glycolysis (TLG) as well as whole-body MTV and whole-body TLG were computed. RESULTS: Twenty-five women were included with a mean age of 43.44 ± 10.32. The majority of the patients were HIV infected with a median CD4 count of 444.00 cells/mm3. The HIV-infected women are younger at diagnosis than their HIV-uninfected counterparts. All patients presented with inguinofemoral lymph node involvement, whereas half the patients had pelvic nodal metastasis. All the patients with distant visceral or skeletal metastasis were HIV infected. The lungs were the most common site of distant metastasis. When comparing the SUVmax, SUVmean, MTV, TLG, wbMTV, and wbTLG between HIV-infected and HIV-uninfected patients, we did not find statistical differences. Twelve patients (48%) were upstaged to metastatic disease. Seven patients had died at the time of analysis. The wbMTV and wbTLG were significantly higher in nonsurvivors than survivors. CONCLUSIONS: 18F-FDG PET/CT improves initial staging of squamous cell carcinoma among women with and without HIV infection. The whole-body tumor burden assessed by 18F-FDG PET metabolic metrics did not differ between HIV-infected and HIV-uninfected women. A higher whole-burden tumor burden is associated with a higher risk of mortality among women with vulva cancer.

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.

Diagnostic value of sentinel lymph node scintigraphy and 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in the detection of metastatic lymph nodes in patients with early-stage cervical cancer.

Cervical cancer is staged clinically using the International Federation of Gynaecology and Obstetrics staging system. Although lymph node status does not form part of the staging, it has important prognostic and potential therapeutic implications. The aim of the study was to evaluate the role of sentinel lymph node (SLN) scintigraphy and 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in detecting lymph node metastases in patients with early-stage cervical cancer. Thirty-six patients with early-stage cervical cancer underwent SLN detection during primary operation. Of the 36 patients, 28 patients underwent 18F-FDG PET/CT before surgery. The 18F-FDG PET/CT images were analyzed with the histopathological findings as the reference standard. The diagnostic performance of 18F-FDG PET/CT in the detection of nodal disease was reported in terms of accuracy value. The SLN detection rate was the highest (91.7%) using the combined method (lymphoscintigraphy, intraoperative gamma probe, and blue dye). Seven of the thirty-six patients had lymph node involvement (19.4%), of which five had preoperative 18F-FDG PET/CT imaging. On overall patient-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of 18F-FDG PET/CT were 40.0%, 78.3%, 28.6%, 85.7%, and 71.4%, respectively. The combination of radiolabeled nanocolloid with blue dye is safe and reliable and allows successful detection of SLNs in patients with early-stage cervical cancer in a population with high prevalence of human immunodeficiency virus. The specificity and NPV of 18F-FDG PET/CT are high and can be used in conjunction with SLN biopsy.

FDG PET/CT for evaluating systemic arterial inflammation induced by anthracycline-based chemotherapy of Hodgkin lymphoma: A retrospective cohort study.

To evaluate arterial fluorodeoxyglucose (FDG) uptake as a marker of arterial inflammation in multiple vascular beds in patients treated with anthracycline-based chemotherapy for Hodgkin lymphoma (HL).We used maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) to quantify arterial FDG uptake in the carotid artery, ascending aorta, abdominal aorta, and femoral artery obtained on positron emission tomography/computed tomography (PET/CT) imaging performed at baseline before chemotherapy and after completion of chemotherapy in patients with HL treated with an anthracycline-containing regimen. We compared the SUVmax and TBR obtained at baseline with that obtained post-chemotherapy for each arterial bed to evaluate the effect of anthracycline-based chemotherapy. We evaluated the effect of cardiovascular risk factors such as human immunodeficiency virus (HIV) infection, smoking, hypertension, and diabetes on the changes in SUVmax and TBR seen in the different arterial beds after anthracycline-based chemotherapy.Fifty-two patients were included with a mean age of 34.56 ±â€Š10.19 years. There were 33 males, and 18 patients were HIV-infected. The mean interval between completion of chemotherapy and follow-up flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan was 65 weeks. We found no significant difference in arterial FDG uptake measured by SUVmax and TBR in all arterial beds between the pre- and post-chemotherapy FDG PET/CT. There was no significant impact of HIV infection, smoking, and hypertension on the changes in arterial FDG uptake following treatment with anthracycline-based chemotherapy.In patients with HL who were treated with anthracycline-based chemotherapy, we found no significant increase in arterial inflammation measured by FDG PET/CT after an average follow-up period of about 65 weeks since completion of chemotherapy.

18F-FDG PET/CT imaging of vulva cancer recurrence: A comparison of PET-derived metabolic parameters between women with and without HIV infection.

OBJECTIVE: To assess the patterns of recurrence of vulva cancer on 18F-FDG PET/CT and to compare the 18F-FDG PET metabolic metrics in patients with and without Human Immunodeficiency Virus (HIV). METHODS: Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumour volume (MTV and total lesion glycolysis (TLG) were obtained on Flourine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) images of women referred with suspected or confirmed vulva cancer recurrence. We compared HIV-infected and HIV-uninfected patients regarding pattern disease recurrence, age at diagnosis, and the PET-derived metabolic indices. RESULTS: We analyzed 33 patients with a mean age 50.76 ± 15.78 including 21 HIV-infected women. The majority of patients (94 %) had squamous cell carcinoma and 84.85 % were Blacks. Of the HIV-infected individuals, the median CD4 count was 526.0 cells/mm3 (IQR: 379.0-729.0). HIV infected patients were younger than the HIV uninfected at the time of diagnosis: 40.50 ±â€Š8.87 vs 66.54 ±â€Š9.71 respectively, p < 0.001. We found a local (vulvar) recurrence rate of 75.8 %. Nodal pelvic recurrences were higher in the HIV-infected patients than in the HIV uninfected patients (70 % vs 30 %, p = 0.027). Three patients had distant metastasis and all three were HIV-infected. There was a higher whole-body MTV and TLG among HIV-infected women compared with HIV-uninfected women, 103.39 vs 17.58 and 852.64 vs 101.79, respectively (p < 0.05 for both). CONCLUSION: HIV-infected women are diagnosed with vulva cancer at a younger age. HIV-infected patients had a higher rate of pelvic lymph node recurrence. There is a higher tumor burden at vulva cancer recurrence among women with HIV infection.

18F-FDG PET/CT as a Noninvasive Biomarker for Assessing Adequacy of Treatment and Predicting Relapse in Patients Treated for Pulmonary Tuberculosis.

Microbial culture is the gold standard for determining the effectiveness of tuberculosis treatment. End-of-treatment (EOT) 18F-FDG PET/CT findings are variable among patients with negative microbial culture results after completing a standard regimen of antituberculous treatment (ATT), with some patients having a complete metabolic response to treatment whereas others have residual metabolic activity (RMA). We herein determine the impact of findings on EOT 18F-FDG PET/CT on tuberculosis relapse in patients treated with a standard regimen of ATT for drug-sensitive pulmonary tuberculosis (DS-PTB). Methods: Patients who completed a standard regimen of ATT for DS-PTB and were declared cured based on a negative clinical and bacteriologic examination were prospectively recruited to undergo EOT 18F-FDG PET/CT. Images were assessed for the presence of RMA. Patients were subsequently followed up for 6 mo looking for symptoms of tuberculosis relapse. When new symptoms developed, relapse was confirmed with bacteriologic testing. Repeat 18F-FDG PET/CT was done in patients who relapsed. Results: Fifty-three patients were included (mean age, 37.81 ± 11.29 y), with 62% being male and 75% HIV-infected. RMA was demonstrated in 33 patients (RMA group), whereas 20 patients had a complete metabolic response to ATT (non-RMA group). There was a higher prevalence of lung cavitation in the RMA group (P = 0.035). The groups did not significantly differ in age, sex, presence of HIV infection, body mass index, or hemoglobin level (P > 0.05). On follow-up, no patients in the non-RMA group developed tuberculosis relapse. Three patients in the RMA group developed relapse. All patients who developed tuberculosis relapse had bilateral disease with lung cavitation. Conclusion: A negative EOT 18F-FDG PET/CT result is protective against tuberculosis relapse. Nine percent of patients with RMA after ATT may experience tuberculosis relapse within 6 mo of completing ATT. Bilateral disease with lung cavitation is prevalent among patients with tuberculosis relapse.

Predictors of Overall and Disease-Free Survival in Metastatic Castration-Resistant Prostate Cancer Patients Receiving 225Ac-PSMA-617 Radioligand Therapy.

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment. Methods:225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps < 0.05). In multivariate analyses, there was a negative association between prior 177Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.

68Ga-PSMA: a One-stop Shop in Radioactive Iodine Refractory Thyroid Cancer?

We report a case of a 47-year-old female known with metastatic papillary thyroid cancer. Her treatment history included total thyroidectomy and 3 previous radio ablations with a cumulative dose of 950 mCi of 131I. On follow-up, her thyroglobulin levels had demonstrated a rising trend (from 3789.0 to 4240.0 ug/L) despite a 123I whole-body scan demonstrating a reduction in tracer avid lesions. She was suspected of having radio-resistant disease. The patient underwent both 18F-FDG and 68Ga-PSMA PET/CT imaging with both scans demonstrating congruent lesions however with far greater intensity on the 68Ga-PSMA study.

Correction to: 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study.

The author of this article wanted to change the ethical approval statement of the originally published version of this article. Correct statement is indicated below.

Fluorodeoxyglucose Positron Emission Tomography integrated with computed tomography in carcinoma of the cervix: Its impact on accurate staging and the predictive role of its metabolic parameters.

OBJECTIVES: To determine the impact of FDG-PET/CT in the initial staging of cervical cancer among women with and without HIV and to determine the abilities of FDG-PET/CT metabolic parameters in predicting the presence of distant metastasis. METHODS: We reviewed the FDG-PET/CT images of women with FIGO stage IB2 to IVA carcinoma of the cervix. We compared the FIGO stage before and after FDG-PET/CT. Maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were determined. We compared these parameters between the HIV-infected and uninfected woman and also determined their abilities to predict the presence of distant metastasis. RESULTS: 126 women, mean age 48.05 ± 11.80 years were studied. Seventy-three patients were HIV-infected. The disease was upstaged in 65 patients, 32 of which were upstaged to stage IVB. HIV-infected women were younger (43.36 ± 8.03 years versus 54.51 ± 13.12, p<0.001) and had more advanced disease (p = 0.022) compared with HIV-uninfected. In a univariate logistic regression adjusted for the FIGO stage of the disease, there were significant associations between MTV and TLG of the primary tumor and distant metastasis. SUVmax, SUVmean, MTV and TLG performed well in predicting the presence of distant metastasis with areas under the curves (AUCs) of 0.63, 0.66, 0.80 and 0.77 respectively. These performances improved after adjustment for the FIGO stage of the disease with AUCs of 0.80, 0.79, 0.84 and 0.82 for SUVmax, SUVmean, MTV and TLG respectively. CONCLUSION: Inclusion of 18F-FDG-PET/CT in the pre-therapy assessment of cervical cancer improves the accuracy of staging in about half of the patients. The metabolic parameters of the primary tumor perform well in predicting the presence of distant metastases.

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.

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.

225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study.

BACKGROUND: A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients. We report our experience with 225Ac-PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. METHODS: Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga-PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. RESULTS: Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. CONCLUSIONS: 225Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.