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.

Assessing nuclear medicine practices: a critical evaluation of QUANUM through a quality improvement perspective and its wider relevance.

Quality Management Audits in Nuclear Medicine (QUANUM) is an initiative conceived by the International Atomic Energy Agency to enhance global standards in Nuclear Medicine practices. Acknowledging the intricate regulatory frameworks and the necessity for multidisciplinary collaboration, QUANUM has gained global acceptance, demonstrating widespread implementation and positive impacts on patient care. This manuscript critically evaluates the QUANUM program through the lens of quality improvement (QI), by employing established and validated QI tools. Our analysis identifies areas of conformance, underscores key strengths inherent to QUANUM, and pinpoints further learning opportunities for continuous enhancement. Additionally, we assert that the insights derived from scrutinizing this global project within Nuclear Medicine, have valuable implications for departments aspiring for establishing good quality management systems, thereby contributing to the improvement of patient care.

Lessons from a 3-Year Review of PSMA PET-CT in a Tertiary Setting: Can We Fine Tune Referral Criteria by Identifying Factors Predicting Positivity and Negativity?

AIM OF THE STUDY: To draw inferences from a retrospective evaluation of PSMA PET CT scans performed for the evaluation of biochemical recurrence. MATERIAL AND METHODS: A retrospective analysis of 295 PSMA PET CT scans spanning 3 years between 2020 and 2022 was undertaken. RESULTS: Of 295 PET CT scans, 179 were positive, 66 were negative and 50 had indeterminate findings. In the positive group, 67 had radical prostatectomy and PSMA avid lesions were seen most commonly in pelvic lymph nodes. The remaining 112 positive scans were in the non-radical prostatectomy group; 25 had recurrence only in the prostate, 17 had recurrence involving the prostate bed; 28 had no recurrence in the prostate gland, while 42 had recurrence in the prostate as well as in extra-prostatic sites. Overall, in the non-prostatectomy group, 75% of the population was harboring a PSMA avid lesion in the prostate gland while in the remaining 25% of the population, recurrence did not involve the prostate gland. The majority of indeterminate findings were seen in small pelvic or retroperitoneal lymph nodes or skeletal regions (ribs/others) and in nine patients indeterminate focus was seen in the prostate bed only. Follow-up PSMA PET CT was helpful in prior indeterminate findings and unexplained PSA rise. CONCLUSION: A higher recurrence in the prostate bed while evaluating biochemical recurrence prompts the following: question: should prostatectomy be offered more proactively? Follow-up PSMA PET CT is helpful for indeterminate findings; a PSA rise of 0.7 ng/mL in 6 months can result in positive PSMA PET CT while negative scans can be seen up to a 2 ng/mL PSA rise in 6 months.

The Role of PET-CT-Guided Metabolic Biopsies in Improving Yield of Inconclusive Anatomical Biopsies: A Review of 5 Years in a Teaching Hospital.

Tumour sampling is indispensable to diagnostic and therapeutic decision making. Thus, 18F-FDG PET/CT has the potential to accurately discriminate between viable and non-viable tissues due to its ability to characterise the metabolism of visible tissues. This study's objective was to evaluate the incremental utility of 18F-FDG PET-CT-guided metabolic biopsy in individuals with suspected lesions and a previous negative anatomical biopsy. This study included a total of 190 consecutive patients with probable malignancy and who had experienced a previous unsuccessful anatomical biopsy who underwent PET-CT-guided metabolic biopsy. We retrospectively analysed the patients' medical records and imaging investigations to assess demographics, complications, pathologies, and final clinical diagnoses. Using multivariate logistic regression, correlation between several confounding factors that lead to post-procedural problems was evaluated. Adequate material was obtained in all patients, and 162 (85%) were found to be positive for malignancy with a diagnostic yield of 96.9%. In 25 (13.1%) patients, post-procedural complications were reported, with pneumothorax being the most prevalent issue. In evaluating oncological patients, metabolic biopsy provides a safer alternative therapy with a high diagnostic yield and comparable complications. PET-CT, being an essential component of cancer staging, may serve as a one-stop shop for the management of these patients' conditions.

Review of the role of MRI and 18 F-sodium fluoride PET/computed tomography in the characterisation of spinal bone metastases in a cohort of patients with breast cancer.

PURPOSE: The purpose of the study was to compare the diagnostic accuracy and relative usefulness of MRI and 18 F-NaF (sodium fluoride) PET/computed tomography (CT) for detection of spinal bone metastases in a cohort of patients with high-risk breast cancer (BrCa). METHODS: A retrospective study was conducted of patient and lesion-based analyses on 66 consecutive patients (median age, 62.5 years; age range, 33-91 years) who underwent Spinal MRI as well as 18 F-NaF PET-CT for restaging of newly diagnosed recurrent BrCa with no previous bone metastases. Both scans were performed within 20 days of each other. Review of prior images, clinical decisions, multi-disciplinary team discussions and decisions as well as follow-up information including scans and definitive tests was performed at least 12 months after the initial scans. RESULTS: Of the 66 patients reviewed, 26 patients had documented spinal bone metastases on one or both modalities, while 40 patients were considered bone disease free on both modalities and this was confirmed on follow-up. On lesion-based analysis, the findings of 18 F-NaF PET-CT and spinal MRI were concordant in 51 patients (77.3%). In the remaining patients, 18 F-NaF PET/CT detected more lesions in 4 patients (7.6%) and MRI detected more lesions in 10 patients (15.1%). Interestingly, there was a very high, 97 % concordance (64 patients) between spinal MRI and 18 F-NaF PET-CT when staging of spinal bone metastasis was taken into consideration. In one patient MRI identified two spinal bone metastases which were not seen on 18 F-NaF PET/CT; and, in one patient 18 F-NaF PET/CT showed few spinal bone metastases when no lesion was seen on MRI. CONCLUSIONS: Our study showed a high level of concordance between 18 F NaF PET-CT and spinal MRI within the setting of detection of bone lesions in the spine in a cohort of patients with high-risk BrCa. In our opinion, this high level of concordance negates the need to perform both tests although each test may be indicated for slightly different reasons. Further longitudinal studies across a longer duration and more centres may provide more definitive answers.

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma.

PURPOSE: Ac-225 labeled with prostate-specific membrane antigen (PSMA-617), a transmembrane glycoprotein which is highly expressed in prostate carcinoma cells, is presently being considered a promising agent of targeted alpha therapy for the treatment of patients suffering from metastatic castration-resistant prostate cancer. In the present study, we report an optimized protocol for the preparation of therapeutic dose of Ac-225 PSMA-617 with high yield and radiochemical purity (RCP). METHODS: Ac-225 PSMA-617 was prepared by adding the peptidic precursor-PSMA-617 (molar ratios, Ac-225: PSMA-617 = 30:1) in 1 ml ascorbate buffer to Ac-225 and heating the reaction mixture at 90°C for 25 min to obtain the radiopeptide with high RCP and yield. The radiolabeled peptide was administered in patients who met the eligibility criteria and posttherapy assessment was done. RESULTS: Ten batches of Ac-225 PSMA-617 were prepared following this protocol. The radiopeptide was obtained with an adequate yield of 85%-87% and RCP of 97%-99%. CONCLUSION: The current protocol allows single-step, successful, routine inhouse radiolabeling of Ac-225 with PSMA-617 with high yield and RCP.

Therapeutic efficacy of 225Ac-PSMA-617 targeted alpha therapy in patients of metastatic castrate resistant prostate cancer after taxane-based chemotherapy.

OBJECTIVES: 225Ac-PSMA-617 therapy has shown good response in many recent studies. We report our experience of targeted alpha therapy with 225Ac-PSMA-617 in mCRPC patients who have failed therapy with taxanes. MATERIALS AND METHODS: Thirty-eight patients with CRPC with progressive disease following at least one taxane-based chemotherapy received 225Ac-PSMA-617 between July 2017 and Nov 2019. Primary end point was a composite 50% PSA and radiological response. Secondary endpoints were PFS, OS, and changes in QOL. The differences in outcomes between patients with skeletal and lymph-node metastases versus those with visceral metastases were also studied. RESULTS: A composite response by predetermined criteria was observed in 25 (66%) of 38 patients. The median PFS was 8 months (95% CI 5.3-10.6 months). Median overall survival was 12 months (95% CI 9.1-14.9) with 16 patients alive at the time of censorship. There was no difference in response rates or survival statistics between patients with visceral metastases versus those with only bone and lymph-node metastases (Chi-square 1.51, df 1, Sig 0.218). The most common adverse effect was xerostomia. On the QOL Symptom score, Pain, Fatigue Insomnia, and constipation showed a significant improvement as compared to baseline. CONCLUSIONS: 225Ac-PSMA-617 is a safe and tolerable treatment option for mCRPC that demonstrates marked anti-tumour activity with improvement in quality of life even in patients of metastatic CRPC who have been previously treated with taxane-based chemotherapy.

Incremental Value of Ga-68 Prostate-Specific Membrane Antigen-11 Positron-Emission Tomography/Computed Tomography Scan for Preoperative Risk Stratification of Prostate Cancer.

BACKGROUND: Prostate cancer (PC) is the second-most common cause of cancer.68Ga-prostate-specific membrane antigen (PSMA)-11 positron-emission tomography/computed tomography (PET/CT) scan help in accurate staging of PC owing to its high PSMA avidity and specificity. The aim of this prospective observational study was to determine the incremental value of Ga-68 PSMA-11 PET/CT over multiparametric magnetic resonance imaging (mpMRI) in the locoregional staging of intermediate- and high-risk PC using histopathology from radical prostatectomy specimens as a gold standard. MATERIALS AND METHODS: This was a prospective study, including 35 patients with biopsy-proven prostate carcinoma. All the patients underwent whole-body Ga-68 PSMA-11 PET/CT scans along with mpMRI including a dedicated pelvic imaging protocol within a time window of ± 10 days. The reference standard was based on histopathological results, postprostatectomy. RESULTS: All 35 patients showed Ga-68 PSMA-11-avid disease, of which 29 underwent radical prostatectomy, one underwent radiation therapy, and five did not undergo surgery owing to metastases. A total of 52 PC lesions were detected in 29 patients on histopathology. Of 52 lesions, 29 lesions were identified in prostate parenchyma and 23 were extraprostatic lesions on histopathology. Ga-68 PSMA-11 PET/CT detected a total of 45 lesions, of which 29 lesions were located within the prostate parenchyma and 16 were representative of extraprostatic lesions. mpMRI detected a total of 36 lesions, of which 29 lesions were located within the prostate parenchyma and seven were representative of extraprostatic lesions. The overall sensitivity of 68Ga-PSMA PET/CT and mpMRI in the detection of lesions was 86.2% and 68.6%, respectively. However, the overall specificity was 94.7% and 89.1% for 68Ga-PSMA and mpMRI, respectively. CONCLUSION: Ga-68 PSMA-11 PET/CT provided superior locoregional preoperative staging of PC as compared to mpMRI in intermediate- and high-risk PC patients.

Radiation Exposure to the Nuclear Medicine Personnel During Preparation and Handling of 213Bi-Radiopharmaceuticals.

Because of the excellent ability of α-particles to transfer a high amount of energy over a short tissue range, targeted α-therapy has been attracting rising numbers of nuclear medicine centers. In this study, we estimated the radiation exposure to the occupational workers with pocket dosimeters during handling of the α-emitter 213Bi, used for targeted α-therapy of neuroendocrine tumor and castration-resistant prostate cancer patients. The dose rates from patients at different distances and time points after injection of the therapy were also evaluated. Methods: This prospective study was done in the Department of Nuclear Medicine at Fortis Memorial Research Institute, Gurgaon, India. Twelve patients with neuroendocrine tumors or castration-resistant prostate cancer were enrolled to receive 213Bi-DOTATOC or 213Bi-prostate-specific membrane antigen therapy, respectively. Each patient received 2-3 intravenous injections of 213Bi-peptide, 266-362 MBq (7.2-9.8 mCi) in a single cycle over 2-3 d. The radiation exposure to nuclear medicine personnel at the chest and extremity levels was assessed for tasks such as elution, dispensing, injecting, and collecting blood samples. Radiation levels were measured at distances of 1 cm and 1 m from patients immediately after, and at 1, 2, and 4 h after, the administration of 213Bi-peptide. Results: The external dose incurred at the chest level by radiopharmacists during synthesis, by physicians during injection, by technologists during imaging, and by nurses during sample collection was 2-7 µSv/procedure. The extremity dose was 1-14 µSv/procedure. The dose rate at 1 m from patients immediately after 213Bi-radiopharmaceutical injection was 0.02-0.03 µSv/MBq⋅h. Conclusion: The external radiation doses received by occupational workers involved in various procedures were far below the limit prescribed by the regulatory authority (20 mSv/y).

Molecular Imaging to the Surgeons Rescue: Gallium-68 DOTA-Exendin-4 Positron Emission Tomography-Computed Tomography in Pre-operative Localization of Insulinomas.

BACKGROUND: Insulinoma is an islet-cell neoplasm that secretes insulin. It is usually localized to the pancreas and is often the most common cause of endogenous hyperinsulinemic hypoglycaemia in non-diabetic adult patients. Surgical excision with a curative intent is the standard modality of treatment, and it requires precise localization of tumor tissue. Ga-68 DOTA-exendin-4 PET/CT scan is a clinically reasonable and sensitive scan for the identification of insulinoma. The aim of this prospective cohort study was to determine the overall accuracy of Ga-68 DOTA-exendin-4 PET/CT scan in the detection of insulinoma. MATERIALS AND METHODS: Eight patients with fasting hyperinsulinemic hypoglycaemia with neuroglycopenic symptoms were enrolled in this study which was conducted during October 2016 to October 2017. Whole body PET/CT scan was performed on a Philips time of flight PET/CT scanner, 60 minutes after injection of Ga-68 DOTA-exendin-4 (and also Ga-68 DOTANOC). The imaging findings were compared to the histopathological diagnosis in six out of eight patients and to subsequent follow up in the remaining two patients who did not undergo surgery. RESULTS: The sensitivity of Ga-68 DOTA-Exendin-4 PET/CT scan in insulinoma detection was found to be 75%. CONCLUSION: Ga-68 DOTA-Exendin-4 PET/CT scan is highly sensitive for identification and exact localization of insulinoma which can guide better surgical exploration. However, randomised controlled trials are needed to assess the accuracy of Ga-68 DOTA-Exendin PET/CT scan in localization of insulinoma.

Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treated with PRCRT (peptide receptor chemo radionuclide therapy) using Lu-177 DOTATATE and capecitabine/temozolomide (CAP/TEM).

OBJECTIVE:: Two radiosensitizing chemotherapeutic drugs, capecitabine (CAP) and temozolomide (TEM), are administered concurrently to enhance the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT). This study aims to assess the biodistribution and normal-organ and tumor radiation dosimetry for Lu-177 DOTATATE administered concurrently with CAP/TEM. METHODS:: 20 patients with non-resectable histologically confirmed gastroenteropancreatic neuroendocrine tumors with normal kidney function, a normal haematological profile and somatostatin receptor expression of the tumor lesions, as scintigraphically assessed by a Ga-68 DOTANOC scan, were included in two groups-case group (n = 10) and control group (n = 10). Patients included in case group were those who were advised concomitant CAPTEM therapy by the treating medical oncologist. Patients were administered CAP orally at a dose of 600mg m-2 bovine serum albumin twice a day for 14 days starting 9 days prior to PRRT and oral TEM as a single dose at a dose of 75 mg m-2 was given concurrently for the last 5 days commencing on the day of PRRT (days 9-14). In the control group, patients were treated with Lu-177 DOTATATE only. For PRRT, 6.4 GBq-7.6 GBq (173-207 mCi) of Lu-177 DOTATATE was administered as infusion into each patient over 10-15 min in a solution with positively charged amino acids for renal protection. Dosimetric calculations were done using the HERMES software. RESULTS:: Physiological uptake of Lu-177 DOTATATE was seen in all patients in liver, spleen kidneys, and bone marrow. Radiation absorbed doses (mean ± standard deviation) were obtained as 0.29 ± 0.12 mGy/MBq for kidneys, 0.30 ± 0.18 mGy/MBq for liver, 0.63 ± 0.37 mGy/MBq for spleen, 0.019 ± 0.001 mGy/MBq for bone marrow and 3.85 ± 1.74 mGy/MBq for tumours in the case group and they were 0.31± 0.26, 0.24 ± 0.14, 0.64 ± 0.42, 0.017 ± 0.016, 5.6 ± 11.27 mGy/MBq in kidneys, liver, spleen, bone marrow and neuroendocrine tumour, respectively, in the control group. Mann-Whitney U test between the variables of two groups showed an insignificant difference (p > 0.05). CONCLUSIONS:: The authors demonstrated no significant difference between the tumor and organ doses with Lu-177 DOTATATE in the patients treated with and without concomitant chemotherapy. ADVANCES IN KNOWLEDGE:: To our knowledge, this is the first dedicated study exhibiting dosimetric analysis in patients undergoing PRRT in combination with chemotherapy.

Radiation Dose to the Occupational Worker during the Synthesis of 188Re-labeled Radiopharmaceuticals in the Nuclear Medicine Department.

AIM: The aim of this study is to estimate whole-body radiation dose to the radiopharmacist involved in labeling of three different 188Re-labeled compounds, namely, 188Re-Lipiodol, 188Re-tin colloid, and 188Re-hydroxyl-ethylidene-diphosphonate (HEDP) and to compare the occupational burden with the dose limits recommended by Atomic Energy Regulatory Board, India. MATERIALS AND METHODS: The Department of Nuclear Medicine at Fortis Memorial Research Institute currently synthesizes three different Rhenium-188 labeled compounds, namely, 188Re-Lipiodol, 188Re-HEDP, and 188Re-tin colloid. To estimate the radiation exposure to the radiopharmacist involved in the synthesis, a survey meter was used to measure radiation level before the start of labeling procedure in the radiopharmacy by keeping it at the location where the radiopharmacist normally stands during preparation. Data were collected for 6 syntheses of each 188Re-Lipiodol, 4 for 188Re-HEDP, and 3 for 188Re-tin colloid followed by the quality control. The pocket dosimeter was used by the radiopharmacistat chest level, performing the labeling of 188Re-labeled compounds. All radiopharmaceuticals were synthesized by a single radiopharmacist. RESULTS: 1850 MBq (50 mCi) 188W-188Re generator was eluted before the preparation of each radiopharmaceutical. The amount of 188ReO4- used for labeling with lipiodol/4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol, HEDP, and Tin colloid was in the range of 3182-4440 MBq (86-120 mCi), 2812-3774 MBq (76-102 mCi), and 962-1295 MBq (26-35 mCi), respectively. Meantime required to complete the synthesis was 95, 40, and 131.5 min, respectively. Mean whole-body effective dose received was 0.052, 0.009, and 0.004 mSv, respectively, as measured by using the pocket dosimeter. CONCLUSION: From this small study, we observed that the whole-body radiation dose to the radiopharmacist in radiolabeling and quality control of 188Re-labeled radiopharmaceuticals is within prescribed limits at the current synthesis frequency.

Rare Sites of Metastases in Prostate Cancer Detected on Ga-68 PSMA PET/CT Scan-A Case Series.

Ga-68 labeled prostate-specific membrane antigen (PSMA) whole body PET/CT scan is a novel upcoming modality for the evaluation of prostate cancer. We present three cases of prostate cancer showing rare sites of metastases like brain, penis, and liver detected on Ga-68 PSMA PET/CT scan thus emphasizing its role in lesion detection and staging.

Comparing SUV values of images at PET-CT console and the RT planning console using identical dataset of a study phantom.

PURPOSE: The use of positron emission tomography (PET) for radiotherapy planning purposes has become increasingly important in the last few years.In the current study, we compared the SUV values of images at the PET CT console to the SUV values obtained at the RT planning workstation. MATERIALS AND METHODS: The PET-CT cylindrical body phantom was filled with a uniform 18F solution of 5.3. ± 0.27 kBq/mL radioactivity concentration. PET-CT scans were performed on a16 slice Time of Flight system. On a single day, the three consecutive scans were done at three time points 15 minutes apart to generate time points image data sets titled T1, T2, and T3. SUV calculations were performed by drawing region of interest. (ROI) encompassing the entire hot spot on each slice on the PET-CT console and the iPlan workstation. Minimum SUV, Maximum SUV and the Mean SUV were recorded. Statistical analysis was done using the SPSS software. (SPSS Inc.) (Version 18). RESULTS: The absolute difference in average max SUV values i.e. Max (PET-CT) - Max (iPlan) for the time points T1, T2 and T3 were -0.168 (SD 0.175), -0.172 (SD 0.172) and -0.178 (SD 0.169). The difference in the minimum SUV values were -0.513 (SD 0.428), -0.311 (SD 0.358) and -0.303 (SD 0.322), respectively. Finally, the difference in the mean SUV values were -0.107 (SD 0.040), -0.096 (SD 0.067) and -0.072 (SD 0.044), respectively. CONCLUSIONS: Our study found out that the average difference in the two systems for maximum SUV values was < 0.2 absolute units.Our study suggests good reproducibility of SUV between the two systems. The relevance of these findings would be of seminal importance in current and future SUV-based PET-CT-based contouring in treatment planning systems.

Role of ¹8F-FDG PET CT as an independent prognostic indicator in patients with hepatocellular carcinoma.

OBJECTIVES: The aim of the study was to evaluate the role of F-fluorodeoxyglucose PET computed tomography (F-FDG PET CT) as an independent prognostic indicator in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PET contrast-enhanced CT scans of 100 consecutive patients with HCC were reviewed retrospectively. Patients were asked to fast for 6 h before the study and blood glucose levels were monitored and ensured to be less than 200 mg/dl before injection of F-FDG. After administering the F-FDG injection (370-550 MBq) patients were instructed to rest comfortably for 45-60 min. All images were acquired using a dedicated GE Discovery PET/CT scanner. The PET CT scans of all the patients were reported separately by two nuclear medicine physicians. A stage-wise analysis of the compiled data was carried out. Lesions that showed standardized uptake values greater than background activity (activity in adjacent normal liver tissue) were defined as having increased F-FDG uptake. Pearson's χ -test or the Kruskal-Wallis test was used to assess statistical significance. A P value less than 0.05 was taken as significant. RESULTS: In this retrospective study of 100 HCC patients, a radiologically higher-stage disease was found more commonly in patients with F-FDG-avid primary tumors (P<0.001), whereas a lower-stage disease was found in patients with non-F-FDG-avid primary tumors. The non-F-FDG-avid tumors also showed lower incidence of metastatic disease and portal vein thrombosis (P<0.001). The histopathological findings of the patients who underwent liver transplantation demonstrated that a higher-grade tumor was more common in the F-FDG-avid tumor group than in the non-F-FDG-avid tumor group (P<0.05). CONCLUSION: An F-FDG PET CT scan can be used not only for staging but also as a tool for preoperative prediction of cellular differentiation in patients with HCC. The F-FDG uptake seen on a PET scan can serve as a molecular signature for management decisions and can be used as an independent and significant prognostic factor in patients with HCC.