Staging Prostate Cancer with 68Ga-PSMA-11 PET/CT in the Elderly: Is Preimaging Biopsy Imperative?

Although prostate-specific membrane antigen (PSMA) PET/CT has been shown valuable for staging biopsy-proven [B(+)] high-risk prostate cancer, elderly patients are occasionally referred for PSMA PET/CT without a preimaging confirming biopsy [B(-)]. The current study evaluated the rate, clinical characteristics, and PET-based stage of elderly B(-) patients and explored whether biopsy status affects therapeutic approach. Methods: One hundred consecutive patients at least 80 y old who underwent staging 68Ga-PSMA-11 PET/CT were included. For each patient, we documented whether preimaging biopsy was performed, the clinical parameters, the PET-based staging parameters, and the primary therapy received. Results: Thirty-four (34%) of the elderly patients included in the study had no preimaging biopsy. Compared with B(+) patients, B(-) patients were older (median age, 87 vs. 82 y; P < 0.01), with worse performance status (P < 0.01) and higher prostate-specific antigen (PSA) levels (median, 57 vs. 15.4 ng/mL; P < 0.01). On 68Ga-PSMA-11 PET/CT, all B(-) patients had avid disease, with trends toward higher rates of bone metastases (47.1% vs. 28.8%) and overall advanced disease (50% vs. 33.3%) than in B(+) patients. Among patients with localized (n = 36) or locally advanced (n = 25) disease, B(-) patients were less commonly referred than B(+) patients for definitive therapies (P < 0.01). However, higher age, Eastern Cooperative Oncology Group performance status, and PSA were other probable factors determining their therapeutic approach. Among 39 patients with advanced disease, 38 received hormonal therapy irrespective of their biopsy status. Among B(-) patients with advanced disease who were referred for hormonal therapy, 12 of 13 with follow-up data showed a biochemical or imaging-based response. Conclusion: Real-life experience with 68Ga-PSMA-11 PET/CT indicates that around one third of elderly patients are referred for imaging without a preimaging confirming biopsy. These patients are likely to be older, with a worse clinical status and higher PSA levels. Advanced disease might be more likely to be identified on their 68Ga-PSMA-11 PET/CT images, and if it is, their biopsy status does not preclude them from receiving hormonal therapy.

PET radiotracers for whole-body in vivo molecular imaging of prostatic neuroendocrine malignancies.

Prostatic neuroendocrine malignancies represent a spectrum of diseases. Treatment-induced neuroendocrine differentiation (tiNED) in hormonally treated adenocarcinoma has been the subject of a large amount of recent research. However, the identification of neuroendocrine features in treatment-naïve prostatic tumor raises a differential diagnosis between prostatic adenocarcinoma with de novo neuroendocrine differentiation (dNED) versus one of the primary prostatic neuroendocrine tumors (P-NETs) and carcinomas (P-NECs). While [18F]FDG is being used as the main PET radiotracer in oncologic imaging and reflects cellular glucose metabolism, other molecules labeled with positron-emitting isotopes, mainly somatostatin-analogues labeled with 68Ga and prostate-specific membrane antigen (PSMA)-ligands labeled with either 18F or 68Ga, are now routinely used in departments of nuclear medicine and molecular imaging, and may be advantageous in imaging prostatic neuroendocrine malignancies. Still, the selection of the preferred PET radiotracer in such cases might be challenging. In the current review, we summarize and discuss published data on these different entities from clinical, biological, and molecular imaging standpoints. Specifically, we review the roles that [18F]FDG, radiolabeled somatostatin-analogues, and radiolabeled PSMA-ligands play in these entities in order to provide the reader with practical recommendations regarding the preferred PET radiotracers for imaging each entity. In cases of tiNED, we conclude that PSMA expression may be low and that [18F]FDG or radiolabeled somatostatin-analogues should be preferred for imaging. In cases of prostatic adenocarcinoma with dNED, we present data that support the superiority of radiolabeled PSMA-ligands. In cases of primary neuroendocrine malignancies, the use of [18F]FDG for imaging high-grade P-NECs and radiolabeled somatostatin-analogues for imaging well-differentiated P-NETs is recommended. KEY POINTS: • The preferred PET radiotracer for imaging prostatic neuroendocrine malignancies depends on the specific clinical scenario and pathologic data. • When neuroendocrine features result from hormonal therapy for prostate cancer, PET-CT should be performed with [18F]FDG or radiolabeled somatostatin-analogue rather than with radiolabeled PSMA-ligand. • When neuroendocrine features are evident in newly diagnosed prostate cancer, differentiating adenocarcinoma from primary neuroendocrine malignancy is challenging but crucial for selection of PET radiotracer and for clinical management.

A lesson in humility: the added values of PET-MRI over PET-CT in detecting malignant hepatic lesions.

PURPOSE: The recent introduction of integrated PET-MRI systems into practice seems promising in oncologic imaging, and efforts are made to specify their added values. The current study evaluates the added values of PET-MRI over PET-CT in detecting active malignant hepatic lesions. METHODS: As part of an ongoing prospective study in our institution that assesses the added values of PET-MRI, subjects undergo PET-CT and subsequent PET-MRI after single radiotracer injection. The current study included 97 pairs of whole-body PET-CT and liver PET-MRI scans, of 61 patients (19/61 had ≥ 2 paired scans), all performed with [18F]FDG and interpreted as showing active malignant hepatic involvement. Primary malignancies were of colorectal/biliary/pancreatic/breast/other origins in 19/9/9/7/17 patients. Monitoring response to therapy was the indication in 86/97 cases. When PET-MRI detected additional malignant lesions over PET-CT, lesions size, their characteristics on PET-MRI, and the influence on the final report were recorded. RESULTS: In 37/97 (38.1%) cases, a total of 78 malignant lesions were identified on PET-MRI but not on PET-CT: 19 lesions (11 cases) were identified on PET of PET-MRI but not on PET of PET-CT; 37 lesions (14 cases) were small (≤ 0.8 cm) and identified on MRI only; 22 lesions (12 cases) were > 0.8 cm, had low/no [18F]FDG uptake, but were categorized as viable based on MRI. These 78 lesions caused major effect on final reports in 11/97 (11.3%) cases, changing reported response assessment category (10/86 cases) or defining malignant hepatic disease on staging/restaging scans (1/11 cases). CONCLUSION: PET-MRI offers several advantages over PET-CT in assessing the extent and response to therapy of malignant hepatic involvement. Additional malignant lesions detected on PET-MRI are attributed to superior PET performance (compared with PET of PET-CT), greater spatial resolution provided by MRI, and improved multi-parametric viability assessment. In around one-tenth of cases, findings identified on PET-MRI but not on PET-CT significantly change the final report's conclusion.

Is There a Role for [18F]FDG PET-CT in Staging MALT Lymphoma?

The role of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [18F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT lymphoma. Sixty-six studies were included. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were documented in the "hottest" extranodal and nodal lesions. Extranodal lesions and accompanying nodal disease were detected on PET in 38/66 (57.6%) and 13/66 (19.7%) studies, respectively. Detection rate of extranodal lesions differed significantly between those located in tissues with high/heterogeneous (e.g., stomach) vs low/homogenous (e.g., subcutaneous-tissue, lung) physiologic [18F]FDG-uptake (40.4% vs. 100%, p < 0.01). Nodal lesions had significantly lower SUVmax, MTV and TLG compared with extrandodal lesions in the same patients. Detection and [18F]FDG-avidity of extranodal lesions were higher in patients with advanced, bulky disease and concomitant marrow/nodal involvement. Increased SUVmax of extranodal lesions predicted shorter PFS (HR 1.10, 95% CI 1.01-1.19, p = 0.02). Higher SUVmax and TLG showed trends towards shorter PFS in patients with localized disease. In conclusion, detection rate of extranodal MALT lymphoma lesions located in tissues with low/homogeneous physiologic [18F]FDG-uptake is excellent on [18F]FDG PET-CT. When detected, SUVmax of extranodal lesions may predict PFS.

Staging 68 Ga-PSMA PET/CT in 963 consecutive patients with newly diagnosed prostate cancer: incidence and characterization of skeletal involvement.

PURPOSE: The aim of the study was to elaborate the incidence and type of skeletal involvement in a large cohort of patients with newly diagnosed prostate cancer (PCa) referred for Ga-68 PSMA-11 PET/CT staging in a single center. METHODS: Study cohort included 963 consecutive patients with newly diagnosed PCa referred for Ga-68 PSMA-11 PET/CT study for staging. The incidence of bone involvement, type of bone metastases, and extent of disease were determined and correlated with the ISUP Grade Group (GG) criteria and PSA levels. RESULTS: Bone metastases were found in 188 (19.5%) of 963 patients. Bone metastases were found in 10.7% of patients with PSA < 10 ng/dL and in 27.4% of patients with PSA > 10 ng/dL and in 6.1% of patients with GG ≤ 2/3 and in 8.9% of patients with GG 4/5. In 7.6% of the patients, skeletal involvement was extensive, while 11.9% of patients had oligometastatic disease. Osteoblastic type metastases were the most common type of bone metastases presented in 133 of the patients with malignant bone involvement (70.7%). More than half of them had only osteoblastic lesions (72 patients (38.3%)), while the other (61 patients (32.5%)) had also intramedullary and/or osteolytic type lesions. Intramedullary metastases were found in 97 patients (51.6%), while 41 (21.8%) of them were only intramedullary lesions. Osteolytic metastases were detected in 36 patients (19.2%), of which 8 were only osteolytic lesions. CONCLUSION: Although traditionally bone metastases of PCa are considered osteoblastic, osteolytic and intramedullary metastases are common, as identified on PET with labeled PSMA. Skeletal spread may be present also in patients with GG ≤ 2/3 and PSA < 10 ng/dL.

[THE ROLE OF PSMA PET/CT IN IMAGING PROSTATE CANCER].

INTRODUCTION: Accurate evaluation of the extent of disease in patients with prostate cancer is of great importance in guiding suitable treatment at all disease stages. Conventional imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), which rely on morphological criteria, are limited in assessing the real extent of prostate cancer. In recent years, molecular imaging via PET/CT using small molecules targeting the prostate-specific membrane antigen (PSMA) protein on prostate cancer cells linked to positron emitting isotopes has emerged as a promising diagnostic tool. PSMA PET/CT, with its high sensitivity and specificity, has revolutionized the field of prostate cancer imaging. The main indications for PSMA PET/CT imaging are staging of high-risk patients and evaluation of biochemical failure. In addition, PSMA-targeting particle-emitting radioligands allow targeted therapy in patients with advanced disease, with promising results.

68Ga-PSMA-11 PET/CT Follow-Up of Patients with Prostate Cancer with Bone Metastases Who Had Reduced Bone Density after Androgen Deprivation Therapy.

Bone metastases from prostate cancer (PCa) often show an increase in density on computed tomography (CT) after successful androgen deprivation therapy (ADT). Density may be reduced, however, as the disease progresses or, contrarily, when disease is no longer active. The current study investigated the role of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in differentiating between these two conditions. METHODS: The study cohort included 15 PCa patients with sclerotic/blastic bone metastasis in whom reduction in bone density of metastasis was noted on follow-up 68Ga-PSMA-11 PET/CT after ADT. Each patient had two PET/CT scans. Prior to the first scan, six patients were castration naïve and nine patients were already treated. All patients had ADT between the two PET/CT scans. PET parameters (SUVmax and tumor-to-background ratio), and CT parameters (HUmax) were determined and compared for each lesion on both scans. Patient's response was based on prostate-specific antigen (PSA) levels and appearance of new lesions. The Kolmogorov-Smirnov test was used to evaluate normal distribution of the continuous variables. RESULTS: Post-ADT reduction in bone density was identified in 37 lesions. The mean HUmax was 883.9 ± 175.1 on the first scan and 395.6 ± 157.1 on the second scan (p < 0.001). Twenty-one of the 37 lesions showed no increased tracer uptake on the second PET/CT scan raising the likelihood of a response. The other 16 lesions were associated with increased uptake suggestive of an active resistant disease. Bone density was not different in lesions that no longer showed an increased uptake as compared with those that did. Seven of the study patients responded to therapy, and none of the 16 lesions found in these patients showed increased 68Ga-PSMA-11 uptake. In eight patients with progressive disease, all 12 lesions in five of them showed increased 68Ga-PSMA-11 uptake, there was mixed response in two patients (having two lesions with increased uptake and one without) and although all three lesions no longer showed an increased uptake, new lesions were detected in the eighth patient. CONCLUSION: A decrease in density of bone lesions may reflect clinical progression, or contrarily, a response to therapy in patients with PCa and skeletal involvement treated with ADT. Uptake of 68Ga-PSMA-11 may separate between these two vastly opposing conditions.

68Ga-PSMA is a novel PET-CT tracer for imaging of hepatocellular carcinoma: A prospective pilot study.

Background:68Ga-Prostate Specific Membrane Antigen (68Ga-PSMA), a positron emission tomography (PET) tracer that was recently introduce for imaging of prostate cancer, may accumulate in other solid tumors including Hepatocellular Carcinoma (HCC). The aim of the study was to assess the potential role of 68Ga-PSMA PET-Computed Tomography (CT) for imaging of HCC. Material and Methods: A prospective pilot study in seven patients with HCC with 41 liver lesions: 37 suspected malignant lesions (tumor lesions) and 4 regenerative nodules. For each liver lesion, uptake of 68Ga-PSMA and 18F-FDG uptake were measured [standard uptake value (SUV) and lesion-to-liver background ratios (TBR-SUV)], and correlated with dynamic characteristics (HU and TBR-HU) obtained on contrast enhanced CT data. Immunohistochemistry staining of PSMA in the tumor tissue was analyzed in samples obtained from 5 patients with HCC and compared to control samples from 3 patients with prostate cancer. Results: Thirty-six of the 37 tumor lesions and none of the regenerative nodules showed increased 68Ga-PSMA uptake while only 10 lesions were 18F-FDG avid. Based on contrast enhancement, tumor lesions were categorized into 27 homogeneously enhancing lesions, nine lesions with "mosaic" enhancement composed of enhancing and non-enhancing regions in the same lesion and a single non-enhancing lesion, the latter being the only non-68Ga-PSMA avid lesion. Using the Mann-Whitney test, 68Ga-PSMA uptake was found significantly higher in enhancing tumor areas compared to non-enhancing areas and in contrast, 18F-FDG uptake was higher in non-enhancing areas, P<0.001 for both. 68Ga-PSMA uptake (TBR SUVmax) was found to correlate with vascularity (TBR-HU) (Spearman r=0.866, p<0.001). Immunohistochemistry showed intense intra-tumoral microvessel staining for PSMA in HCC, in contrast with cytoplasmic and membranous staining, mainly in the luminal border, in prostate cancer samples. In two of the study patients 68Ga-PSMA PET-CT identified unexpected extrahepatic metastases. Four regenerative liver nodules showed no increased uptake of either of the PET tracers. Conclusion:68Ga-PSMA PET-CT is superior to 18F-FDG PET-CT in imaging patients with HCC. HCC lesions are more commonly hypervascular taking up 68Ga-PSMA in tumoral micro-vessels. 68Ga-PSMA PET-CT is a potential novel modality for imaging patients with HCC.

The Value of PET/CT in Detecting Bone Marrow Involvement in Patients With Follicular Lymphoma.

Follicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL. In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment. Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7-6] vs 1.4 [0.4-2.65], P < 0.001). On receiver operator curve (ROC) analysis, BM-SUVmean > 2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmean < 1.7 had an NPV of 100% (specificity of 73%). Visual assessment of PET/CT is appropriate for ruling out BM involvement by FL. Although focal increased uptake indicates marrow involvement, diffuse uptake is nonspecific. SUV measurement improves PET/CT diagnostic accuracy, identifying additional 19% of patients with BM involvement that would have been otherwise missed.

(99m)Tc-MDP bone scintigraphy of the hand: comparing the use of novel cadmium zinc telluride (CZT) and routine NaI(Tl) detectors.

BACKGROUND: Cadmium zinc telluride (CZT) solid-state detectors have been recently introduced in the field of nuclear medicine in cardiology and breast imaging. The aim of the current study was to evaluate the performance of the novel detectors (CZT) compared to that of the routine NaI(Tl) in bone scintigraphy. A dual-headed CZT-based camera dedicated originally to breast imaging has been used, and in view of the limited size of the detectors, the hands were chosen as the organ for assessment. This is a clinical study. METHODS: Fifty-eight consecutive patients (total 116 hands) referred for bone scan for suspected hand pathology gave their informed consent to have two acquisitions, using the routine camera and the CZT-based camera. The latter was divided into full-dose full-acquisition time (FD CZT) and reduced-dose short-acquisition time (RD CZT) on CZT technology, so three image sets were available for analysis. Data analysis included comparing the detection of hot lesions and identification of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints. RESULTS: A total of 69 hot lesions were detected on the CZT image sets; of these, 61 were identified as focal sites of uptake on NaI(Tl) data. On FD CZT data, 385 joints were identified compared to 168 on NaI(Tl) data (p < 0.001). There was no statistically significant difference in delineation of joints between FD and RD CZT data as the latter identified 383 joints. CONCLUSIONS: Bone scintigraphy using a CZT-based gamma camera is associated with improved lesion detection and anatomic definition. The superior physical characteristics of this technique raised a potential reduction in administered dose and/or acquisition time without compromising image quality.