Advances in PSMA Alpha Theragnostics.

Alpha theranostics offer an attractive alternative form of therapy, which has best been investigated and documented with 225Ac-PSMA in patients with prostate cancer. Advantages offered by targeted alpha therapy include overcoming radiation resistance, oxygen independence, effecting double-stranded DNA breakages within the tumors with anticipated improved clinical outcomes and an acceptable side effect profile. The previous Seminars article on this topic, published in 2020, had to rely mostly on published case reports and small observational studies. In the last few years, however, several meta-analyses have emerged that evaluate the safety and efficacy of 225Ac-PSMA in prostate cancer patients, followed most recently by a multi-center retrospective study initiated by WARMTH. The findings of these publications, together with the exploration of TAT offered in clinical conditions other than as a last resort, is the focus of this updated overview. Unresolved clinical issues that remain, include the appropriate selection of patients that would benefit most from treatment with 225Ac-PSMA, treatment timing within the disease landscape, optimal dosing schedule, dosimetry, when and how to best use combination therapies and minimization and treatment of side effects, particularly that of xerostomia.

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA.

BACKGROUND: Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30-90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. METHODS: This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. RESULTS: The median SRF of the right kidney was 49.9% (range: 3-91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0-94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. CONCLUSIONS: PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

Correlation between [68Ga]Ga-FAPI-46 PET Imaging and HIF-1α Immunohistochemical Analysis in Cervical Cancer: Proof-of-Concept.

Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1α). [68Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [68Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1α expression. The [68Ga]Ga-FAPI PET/CT scans of women with cancer of the cervix were reviewed and the maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. Correlation analysis was performed between PET-derived parameters and immunohistochemical staining as well as between PET-derived parameters and the presence of metastasis. Ten women were included. All patients demonstrated tracer uptake in the primary site or region of the primary. All patients had lymph node metastases while only six patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI-TV was 18.89, 6.88, and 195.66 cm3, respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1α expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1α (r=0.80;p=0.017). The presence of skeletal metastasis was correlated to the HIF-1⍺ staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax.

Expanding radiotherapy access in Sub-Saharan Africa: an analysis of travel burdens and patient-related benefits of hypofractionation.

Purpose: The purpose of this project was to examine the travel burdens for radiotherapy patients in Nigeria, Tanzania, and South Africa, and to assess the patient-related benefits of hypofractionated radiotherapy (HFRT) for breast and prostate cancer patients in these countries. The outcomes can inform the implementation of the recent Lancet Oncology Commission recommendations on increasing the adoption of HFRT in Sub-Saharan Africa (SSA) to enhance radiotherapy access in the region. Methods: Data were extracted from electronic patient records at the NSIA-LUTH Cancer Center (NLCC) in Lagos, Nigeria and the Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, South Africa, from written records at the University of Nigeria Teaching Hospital (UNTH) Oncology Center in Enugu, Nigeria, and from phone interviews at Ocean Road Cancer Institute (ORCI) in Dar Es Salaam, Tanzania. Google Maps was used to calculate the shortest driving distance between a patient's home address and their respective radiotherapy center. QGIS was used to map the straight-line distances to each center. Descriptive statistics were used to compare transportation costs, time expenditures, and lost wages when using HFRT versus conventionally fractionated radiotherapy (CFRT) for breast and prostate cancer. Results: Patients in Nigeria (n=390) traveled a median distance of 23.1 km to NLCC and 86.7 km to UNTH, patients in Tanzania (n=23) traveled a median distance of 537.0 km to ORCI, and patients in South Africa (n=412) traveled a median distance of 18.0 km to IALCH. Estimated transportation cost savings for breast cancer patients in Lagos and Enugu were 12,895 Naira and 7,369 Naira, respectively and for prostate cancer patients were 25,329 and 14,276 Naira, respectively. Prostate cancer patients in Tanzania saved a median of 137,765 Shillings in transportation costs and 80.0 hours (includes travel, treatment, and wait times). Mean transportation cost savings for patients in South Africa were 4,777 Rand for breast cancer and 9,486 Rand for prostate cancer. Conclusion: Cancer patients in SSA travel considerable distances to access radiotherapy services. HFRT decreases patient-related costs and time expenditures, which may increase radiotherapy access and alleviate the growing burden of cancer in the region.

225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings.

PURPOSE: 225Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following 225Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC patients that refused standard treatment options and were treated with 225Ac-PSMA-617. METHODS: We retrospectively reviewed patients with histologically confirmed de novo treatment-naïve bone ± visceral mHSPC that were treated with 225Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate-specific antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities. RESULTS: Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%) had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality and shorter progression-free survival. Overall, administration of 225Ac-PSMA-617 was well tolerated. The commonest toxicity seen was grade I/II dry mouth observed in 94% of patients. CONCLUSIONS: Given these favorable results, randomized prospective multicenter trials assessing the clinical value of 225Ac-PSMA-617 as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.

The Role of PET/CT in Breast Cancer.

Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer worldwide, with an estimated 2.3 million new cases (11.7%), followed by lung cancer (11.4%) The current literature and the National Comprehensive Cancer Network (NCCN) guidelines state that 18F-FDG PET/CT is not routine for early diagnosis of breast cancer, and rather PET/CT scanning should be performed for patients with stage III disease or when conventional staging studies yield non-diagnostic or suspicious results because this modality has been shown to upstage patients compared to conventional imaging and thus has an impact on disease management and prognosis. Furthermore, with the growing interest in precision therapy in breast cancer, numerous novel radiopharmaceuticals have been developed that target tumor biology and have the potential to non-invasively guide the most appropriate targeted therapy. This review discusses the role of 18F-FDG PET and other PET tracers beyond FDG in breast cancer imaging.

The SARS-COV-2 Seroprevalence among Oncology Patients.

Patients with cancer are presumed to be vulnerable to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe clinical outcomes due to the immunocompromised state mediated by their underlying malignancies and therapy. The aim of this study was to estimate the SARS-CoV-2 seroprevalence, following second to fourth waves in solid tumour patients attending the Steve Biko Academic Hospital (SBAH) for diagnosis and treatment of cancer. We used the single-prick COVID-19 IgG/IgM Rapid Test Cassettes to detect SARS-CoV-2 IgG/IgM antibodies in 760 patients with solid tumours who were asymptomatic and who had never tested positive for coronavirus disease 2019 (COVID-19). Out of the 760 patients, 277 were male (36.4%), 483 were female (63.6%), and the mean age was 55 years (range 18−92). The estimated total seroprevalence was 33.2%. The seroprevalence status of the COVID-19 IgG/IgM antibodies rose significantly from the second wave (11.3%) to the third (67.38%) and then the fourth (69.81%) waves with roughly similar counts. A significant number of the seropositive patients were asymptomatic to COVID-19 (96%). There was a higher rate of seropositivity in cancer patients with hypertension (p < 0.05). Patients with breast, gynaecologic, and prostate cancers exhibited increased SARS-CoV-2 seropositivity. Although oncology patients may be susceptible to SARS-CoV-2 infection, our data indicate that these patients remained asymptomatic throughout various waves with an overall COVID-19 IgG/IgM antibody seropositivity of 33.16%, suggesting no risk of severe or fatal cases of COVID-19.

Gallium-68 Labelled Radiopharmaceuticals for Imaging Inflammatory Disorders.

Inflammation is an important component of several chronic and debilitating diseases that result in significant morbidity and mortality. This is best evidenced within the cardiovascular system where it may manifest as atherosclerosis or myocarditis, and at the extreme end of the spectrum as myocardial infarction, ventricular remodeling, or cardiac failure. Early non-invasive detection and monitoring of inflammation in these and other settings may better guide patient management with resultant improved outcomes. Key role players in inflammation pathophysiology include chemokines, macrophages, neutrophils, fibroblasts, integrins, and reactive oxygen species, amongst others. Examples of receptor expression and over-expression include somatostatin receptors, CXCR4-, folate-, mannose-, TSPO- receptors and secretion of various vascular adhesion molecules (such as VCAM and ICAM). Gallium-68-based PET offers imaging possibilities for nearly all the major pathophysiological role players in inflammation, with mounting recent interest in macrophage differentiation, various forms of receptor expression and secretion of chemokines and vascular adhesion molecules. The advantages in terms of logistics and costs of having generator-produced PET probes available is well known, and a 68Ga-based tracer provides easily translatable theranostic possibilities to especially Lu-177. Some of the more versatile and better validated Ga-68-based inflammation probes include 68Ga-DOTA-TATE/NOC/TOC, 68Ga-NOTA-RGD, 68Ga-CXCR4, 68Ga-citrate and 68Ga-FAPI.

Current Status of 68Ga-Pentixafor in Solid Tumours.

Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. 68Ga-Pentixafor is used to non-invasively image the expression of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. 68Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may benefit from novel therapies targeting CXCR4. In addition, its therapeutic partners 177Lu- and 90Y-Pentixather have been investigated in the treatment of patients with advanced haematological malignancies, and initial studies have shown a good treatment response in metabolically active lesions. 68Ga-Pentixafor in solid tumours complements 18F-FDG by providing prognostic information and selecting patients who may benefit from therapies targeting CXCR4. This review summarises the available literature on the potential applications of 68Ga-Pentixafor in solid tumours.

68 Ga-nitroimidazole PET/CT imaging of hypoxia in tuberculosis: A case series.

Tuberculosis (TB) lesions in humans have been proven to be severely hypoxic with hypoxia leading to latency and dormancy of disease. Dormant TB lesions become less susceptible to standard TB treatment regimens with varying responses to treatment but may have increased susceptibility to nitroimidazole drugs. This in turn implies that positron emission tomography / computed tomography (PET/CT) imaging with radiolabelled nitroimidazoles may identify patients who will benefit from treatment with antimicrobial agents that are active against anaerobic bacteria. This case series aims to highlight the hypoxic uptake and retention of a novel 68 Ga-labelled hypoxia-seeking agent in TB lesions at different time points during anti-TB therapy using PET/CT imaging. Patients with confirmed TB underwent whole-body PET/CT after administration of a 68 Ga-nitroimidazole derivative at baseline and follow-up. Images were analysed both qualitatively and semi-quantitatively. Hypoxic uptake and change in uptake over time were analysed using lesion-to-muscle ratio (LMR) and lesion-to-blood ratio (LBR). 68 Ga-nitroimidazole avid lesions were demonstrated most frequently in the upper lobes of the lung. Low-grade hypoxic uptake was visualised in areas of consolidation, cavitation, nodules and lymph nodes. From baseline to follow-up imaging, the LMR increased with persistent hypoxic load despite morphologic improvement. This case series highlights the dynamic hypoxic microenvironment in TB lesions. From these initial data, it appears that 68 Ga-nitroimidazole is a promising candidate for monitoring hypoxic load in patients diagnosed with TB. Such imaging could identify patients who would benefit from individualised therapy targeting other mechanisms in the TB microenvironment with the intention to predict or improve treatment response.

PET/CT features of a novel gallium-68 labelled hypoxia seeking agent in patients diagnosed with tuberculosis: a proof-of-concept study.

INTRODUCTION: Positron emission tomography/computed tomography (PET/CT) in infection and inflammation has yielded promising results across a range of radiopharmaceuticals. In particular, PET/CT imaging of tuberculosis (TB) allows for a better understanding of this complex disease by providing insights into molecular processes within the TB microenvironment. TB lesions are hypoxic with research primarily focussed on cellular processes occurring under hypoxic stress. With the development of hypoxia seeking PET/CT radiopharmaceuticals, that can be labelled in-house using a germanium-68/gallium-68 (68Ge/68Ga) generator, a proof-of-concept for imaging hypoxia in TB is presented. METHODS: Ten patients diagnosed with TB underwent whole-body PET/CT imaging, 60-90 min after intravenous administration of 74-185 MBq (2-5 mCi) 68Ga-nitroimidazole. No oral or intravenous contrast was administered. Images were visually and semiquantitatively assessed for abnormal 68Ga-uptake in the lungs. RESULTS: A total of 28 lesions demonstrating hypoxic uptake were identified. Low- to moderate-uptake was seen in nodules, areas of consolidation and cavitation as well as effusions. The mean standard uptake value (SUVmean) of the lesions was 0.47 (IQR, 0.32-0.82) and SUVmax was 0.71 (IQR, 0.41-1.11). The lesion to muscle ratio (median, 1.70; IQR, 1.15-2.31) was higher than both the left ventricular and the aorta lesion to blood ratios. CONCLUSION: Moving towards the development of unique host-directed therapies (HDT), modulation of oxygen levels may improve therapeutic outcome by reprogramming TB lesions to overcome hypoxia. This proof-of-concept study suggests that hypoxia in TB lesions can be imaged and quantified using 68Ga-nitroimidazole PET/CT. Subsequently, hypoxic load can be estimated to inform personalised treatment plans of patients diagnosed with TB.

68Ga-PSMA-11 PET/CT Initial Staging in Black and White South African Males with ISUP Grade Group 1 and 2 Prostate Adenocarcinoma.

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings.

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.

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.

The Use of 18F-FDG PET/CT Metabolic Parameters in Predicting Overall Survival in Patients Undergoing Restaging for Malignant Melanoma.

Malignant melanoma is one of the more aggressive cancers in the skin, with an increasing incidence every year. Melanoma has a better prognosis if diagnosed early and survival tends to decrease once the disease has metastasized. Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) has been used extensively over the past two decades in staging and assessing responses to therapy in patients with melanoma. Metabolic PET parameters have been demonstrated to be independent prognostic factors for progression-free survival (PFS) and overall survival (OS) in different malignancies, melanoma included. In our study, we evaluated the metabolic parameters of 18F-FDG PET/CT (flourodeoxyglucose positron emission tomography/computed tomography) in predicting the overall survival in patients with malignant melanoma who presented for restaging. Metabolic PET parameters (maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) of the primary tumor, as well as whole-body MTV and TLG of the metastatic disease, were measured. Survival curves for OS were constructed and mortality rates were determined using the different PET variables. Forty-nine patients who presented for a PET/CT restaging in melanoma were included in this study. We found that non-survivors had significantly higher median MTV (11.86 cm3 vs. 5.68 cm3; p-value = 0.022), TLG (3125 vs. 14; p-value = 0.0357), whole-body MTV (53.9 cm3 vs. 14.4 cm3; p-value = 0.0076) and whole-body TLG (963.4 vs. 114.6; p-value = 0.0056). This demonstrated that high MTV and TLG values of the primary tumor and whole-body TLG as quantified by 18F-FDG PET/CT were prognostic factors for overall survival. The findings may potentially guide clinicians in decision making and identifying patients with a poorer prognosis.

A Prospective Investigation of Tumor Hypoxia Imaging with 68Ga-Nitroimidazole PET/CT in Patients with Carcinoma of the Cervix Uteri and Comparison with 18F-FDG PET/CT: Correlation with Immunohistochemistry.

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years 68Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with 68Ga-Nitroimidazole derivative and the correlation with 18F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both 18F-FDG and 68Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for 68Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of 68Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on 68Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on 68Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = -0.660; p = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on 68Ga-Nitroimidazole PET imaging.

mCRPC Patients Receiving 225Ac-PSMA-617 Therapy in the Post-Androgen Deprivation Therapy Setting: Response to Treatment and Survival Analysis.

225Ac-PSMA-617, targeting the prostate-specific membrane antigen (PSMA), which is overexpressed on prostate cancer cells, has shown a remarkable therapeutic efficacy in heavily pretreated patients with metastatic castration-resistant prostate carcinoma (mCRPC). Here, we report on treatment outcome and survival using this novel treatment modality in a series of 53 patients with mCRPC directly after their androgen deprivation treatment (ADT). Methods: 225Ac-PSMA-617 was administered to 53 such patients. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up to select patients for treatment, determine the activity to be administered, and assess their response. Serial prostate-specific antigen (PSA) measurements were obtained for response assessment. Results: The median age of the patients was 63.4 y (range, 45-83 y). In total, 167 cycles were administered (median, 3; range, 1-7). Forty-eight patients (91%) had a PSA decline of at least 50%, and 51 patients (96%) had any decline in PSA. 68Ga-PSMA PET findings became negative in 30 patients. In the multivariate analysis, a PSA decline of at least 50% proved predictive of both progression-free survival (PFS) and overall survival (OS), and platelet count also proved predictive for PFS. The median estimated OS was 9 mo for patients with a PSA decline of less than 50% but was not yet reached at the latest follow-up (55 mo) for patients with a PSA decline of 50% or more. The estimated median PFS was 22 mo for patients with a PSA decline of at least 50% and 4 mo for patients with a PSA decline of less than 50%. No severe hematotoxicity was noted, and only 3 patients had grade III-IV nephrotoxicity. The commonest toxicity seen was grade I-II xerostomia, observed in 81% of patients. Conclusion: In 91% of 53 patients with mCRPC, treatment with 225Ac-PSMA-617 immediately after ADT resulted in at least a 50% decrease in PSA level. Furthermore, a PSA decline of at least 50% proved the single most important factor predicting PFS and OS after 225Ac-PSMA-617 treatment. Of interest, median OS in patients with a PSA decline of at least 50% was not yet reached at the latest follow-up (55 mo). These favorable results suggest that it would be of major clinical relevance to perform a prospective randomized study comparing 225Ac-PSMA-617 with current standard-of-care treatment options such as enzalutamide, abiraterone acetate, and docetaxel after ADT.

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.

The Role of Positron Emission Tomography and Computed Tomographic (PET/CT) Imaging for Radiation Therapy Planning: A Literature Review.

PET/CT is revolutionising radiotherapy treatment planning in many cancer sites. While its utility has been confirmed in some cancer sites, and is used in routine clinical practice, it is still at an experimental stage in many other cancer sites. This review discusses the utility of PET/CT in cancer sites where the role of PET/CT has been established in cases such as head and neck, cervix, brain, and lung cancers, as well as cancer sites where the role of PET/CT is still under investigation such as uterine, ovarian, and prostate cancers. Finally, the review touches on PET/CT utilisation in Africa.

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.