Is 18F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through 18F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations.

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients.

PURPOSE: The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival. METHODS: This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2-9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP). RESULTS: After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1-5) and 2 (1-6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09). CONCLUSION: In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.

Diverse PSMA expression in primary prostate cancer: reason for negative [68Ga]Ga-PSMA PET/CT scans? Immunohistochemical validation in 40 surgical specimens.

PURPOSE: The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [68Ga]Ga-PSMA PET/CT prior to surgery, with special consideration of PET-negative cases. METHODS: The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [68Ga]Ga-PSMA I&T PET/CT as part of the diagnostic work-up prior to radical prostatectomy. All primary tumors were routinely stained with H&E. In addition, immunohistochemical staining of PSMA was performed and the immunoreactive score (IRS) was computed as semiquantitative measure. Subsequently, imaging findings were correlated to histopathologic results. RESULTS: Eighty-three percent (33/40) of patients presented focal uptake of [68Ga]Ga-PSMA I&T in the primary tumor in at least one prostate lobe. Among PSMA-PET positive patients, one-third had lymph node metastases (LNM) detected by post-operative histopathology, while in PET negative patients, only 1 out of 7 presented with regional LN involvement; PSMA-avid distant lesions, predominantly in bones, were observed in 15% and 0% of patients, respectively. The median IRS classification of PSMA expression in tumor tissue was 2 (range, 1-3) both in PSMA-PET positive and negative prostate lobes, with significantly different interquartile range: 2-3 vs. 2-2, respectively (p = 0.03). The median volume of PSMA-PET positive tumors was 5.4 mL (0.2-32.9) as compared to 1.6 mL (0.3-18.3) of PET-negative tumors (p < 0.001). There was a significant but weak correlation between SUVmax and percentage of PSMA-positive tumor cells (r = 0.46, p < 0.001). A total of 35/44 (~80%) lobes were positive in PSMA-PET imaging, when a cut-off percentage of PSMA-positive cells was ≥ 90%, while 19/36 (~53%) lobes with < 90% PSMA-positive cells were PSMA-PET negative. CONCLUSION: Positive [68Ga]Ga-PSMA I&T PET/CT scan of primary tumor of PCa results from a combination of factors, such as homogeneity and intensity of PSMA expression, tumor volume and grade, with a cutoff value of ≥ 90% PSMA-positive cells strongly determining PET-positivity. Focal accumulation of [68Ga]Ga-PSMA in the primary tumor may correlate positively with aggressiveness of prostate cancer, harboring higher risk of regional LN involvement and distant metastatic spread.

Challenging Visualization of Sentinel Lymph Nodes in Upper Urinary Tract Urothelial Carcinoma.

PURPOSE: The purpose of this study was to assess the possibility of detecting sentinel lymph nodes (SLNs) and to perform analysis of lymphatic outflow in patients with suspicion of upper tract urothelial carcinoma (UTUC) with the use of a radioisotope-based technique. METHODS: During 2018-2021, a prospective study was conducted on 19 patients with the suspicion of UTUC and for whom diagnostic ureterorenoscopy (URS) was planned. Technetium-99m (99mTc) nanocolloid radioactive tracer injection and a tumor biopsy were performed for staging procedures. Three-dimensional (3D) reconstruction and fusion of images were performed for better localization of lymph nodes (LNs). Detection of SLNs and the analysis of the radiotracer outflow was conducted with the use of single-photon emission-computed tomography/computed tomography (SPECT/CT) lymphangiography. RESULTS: The mean age of the patients was 73.4 years; 7 (36%) were male. Pathological staging from the biopsy was T0-8 (42%), Ta-7 (36%), T1-4 (21%). SLNs were detected in two of 19 cases (10%). In one patient a single SLN (5.3%) was visualized, and in another case (5.3%), multiple (double) radioactive lymph nodes were visualized. In 17 out of the 19 (89.5%) cases, no lymphatic outflow was observed, and out of these five cases (26.3%) of gravitational leakage of injected radiotracer to the retroperitoneal space was noted. CONCLUSIONS: We demonstrated that detection of SLNs in the upper urinary tract is possible yet challenging. Radiotracer injection in the upper urinary tract during ureterorenoscopy is difficult to perform, and the expected result of injection is unsatisfactory. Lymphatic outflow from the tumor site to the first LNs in our studied group of patients is visible in 10.5% of cases. SPECT/CT lymphangiography in cases of UTUC may provide valuable information about a patient's individual anatomy of the lymphatic system and the position of the first lymph nodes draining lymph with potential metastatic cells from the tumor.

PSMA Theranostics: A "Must Have" in Every Prostate Cancer Center. Illustration of Two Clinical Cases and Review of the Literature.

This manuscript describes the history of 2 patients with prostate cancer (PCa) and the role of prostate-specific membrane antigen (PSMA) theranostics in their clinical management. In the first patient, PSMA-directed positron emission tomography (PET)/computed tomography (CT) imaging was used for primary staging of high-risk PCa before initial therapy. Then after biochemical relapse it was used to plan the scope of further treatment, in which it allowed among others to perform precise target volume delineation for salvage radiotherapy for pathologic lymph nodes. In the second patient with metastatic castration-resistant prostate cancer (mCRPC), PSMA-guided imaging played a key role in the qualification for PSMA-directed radioligand therapy (RLT) with lutetium-177. We also present a review of the current literature concerning PSMA theranostics in the 2 clinical settings, ie, primary staging of PCa and PSMA RLT of mCRPC. In the first part of the review, we report on the diagnostic efficacy of various PSMA imaging radiotracers labeled with gallium-68, fluorine-18, and technetium-99m. In the second part, we describe the limitations and future perspectives of PSMA therapeutic radiopharmaceuticals, including various beta(-) and alpha emitters.

Radionuclide-guided sentinel lymph node mapping in urachal cancer.

BACKGROUND: Urachal cancer gives metastases through the lymph nodes (LNs). No lymphadenectomy scheme in the case of this cancer exist, yet it is proposed as a staging procedure. An assessment of lymphatic outflow from the tumor site with the use of single-photon emission computed tomography/computed tomography (SPECT/CT) lymphangiography is possible for staging purposes. OBJECTIVES: To perform the mapping of the LNs draining the lymph from urachal cancer with the use of radioisotope-based technique and to propose the lymphadenectomy template in case of urachal cancer. MATERIAL AND METHODS: A prospective study was conducted in 5 patients with urachal cancer. The 99m-technetium (Tc-99m)-nanocolloid was injected during a cystoscopy prior to the surgery. Lymphangiography was performed using SPECT/CT. A radioactive LNs analysis with the use of a hand-held gamma-ray detection probe was conducted during the surgery and the sentinel lymph node (SLN) biopsy procedure was performed. An additional lymphadenectomy containing the lymphatic basin of identified radioactive LNs was performed. RESULTS: In all cases lymphatic outflow from the urachal tumor to the LNs was present. Preoperative SPECT/CT allowed detecting the activity of the radiotracer in the common iliac region in all the studied patients. In 3 cases, bilateral lymphatic outflow, and in 2 cases, unilateral lymphatic outflow was observed. All preoperatively visualized LNs were found and excised with the use of a gamma-ray detection probe during a lymphadenectomy. In all cases, SLNs did not contain metastases. CONCLUSIONS: Mapping of the LNs draining the lymph from urachal cancer with the use of radiotracer is possible. Lymphatic outflow in the case of this cancer can be both unilateral and bilateral. No recommendations about the extension of lymphadenectomy are proposed. We recommend individual assessment and treatment based on additional knowledge about lymphatic outflow. This allows for minimally invasive yet targeted treatment as an SLN basin lymphadenectomy.

68Ga-PSMA I&T PET/CT for primary staging of prostate cancer.

PURPOSE: The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA I&T) PET/CT performed in newly diagnosed, treatment-naïve prostate cancer (PCa) patients prior to definitive treatment. METHODS: A total of 82 men were included in the study and were imaged with 68Ga-PSMA I&T PET/CT to assess the distribution of PSMA-avid disease for staging purposes (11 with low-risk, 32 with intermediate-risk, and 39 with high-risk PCa). Forty patients (20 with intermediate- and 20 with high-risk disease) underwent subsequent radical prostatectomy with extended pelvic lymph node dissection which allowed for correlation of imaging findings with histopathologic data. RESULTS: PSMA-positive disease was detected in 83% of patients with 66/82 (80.5%) primary tumours being visualized. PSMA-avid lymph nodes were recorded in 17/82 patients (20.7%, 3 with intermediate-risk and 14 with high-risk PCa); distant disease was found in 14/82 subjects (17.1%, 2 with intermediate-risk and 12 with high-risk PCa). No extraprostatic disease was found in low-risk PCa. SUVmax of primary tumours showed a weak but significant correlation with serum PSA values (r = 0.51, p < 0.001) and Gleason scores (GSC; r = 0.35, p = 0.001), respectively. In correlation with histopathology, calculated per-region sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of lymph node metastases were 35.0%, 98.4%, 63.6%, 95.0%, and 93.0%, respectively. CONCLUSIONS: In patients with initial diagnosis of intermediate- and high-risk prostate cancer, 68Ga-PSMA I&T PET/CT emerges as a relevant staging procedure by identifying nodal and/or distant metastases. Due to the low prevalence of extraprostatic disease, its value seems to be limited in low-risk disease.

Chemokine Receptor 4 Expression in Primary Sjögren's Syndrome.

Ga-pentixafor is a novel radioligand of C-X-C motif chemokine receptor 4. A 55-year-old woman with a history of primary Sjögren's syndrome underwent Ga-pentixafor PET/CT for staging of lymphoma originating from mucosa-associated lymphoid tissue. Whereas no lymphoma manifestation could be detected, imaging revealed bilateral intense radiotracer uptake in both parotid and submandibular salivary glands, consistent with inflammatory cell infiltration.

Fluorescent Versus Radioguided Lymph Node Mapping in Bladder Cancer.

INTRODUCTION: The aim of the study was to compare 2 methods of the sentinel lymph node biopsy (SLNB) procedure in bladder cancer: we applied technetium radiocolloid (RadCol) detected by a gamma ray detection probe, and indocyanine green (ICG) detected by a near-infrared fluorescent (NIRF) camera. MATERIAL AND METHODS: The SLNB was performed on 50 patients using the RadCol and the ICG, followed by a lymphadenectomy and a pathologic examination. RESULTS: In the analyzed group of 47 patients (3 patients were excluded owing to the lack of lymphatic drainage from the tumor), the SLNB was performed using the 2 methods. The ICG with a NIRF-guided camera detected all sentinel lymph nodes (SLNs) in 46 cases, whereas RadCol detected them in 45 cases. In 12 (25.6%) of 47 patients, the ICG-fluorescent method revealed more SLNs than the RadCol method. In 8 (17%) patients, the SLNs revealed in the ICG fluorescence were metastatic. In 3 (6.4%) patients, we found SLNs outside the standard lymphadenectomy template, but a histopathologic examination showed they were negative for cancer. In 3 (6.4%) patients, the SLNs detected by both methods were negative for cancer, but other resected lymph nodes revealed metastases. CONCLUSION: Our study shows that SLNB procedure with the RadCol or the ICG method is useful for the evaluation of lymph nodes in bladder cancer. The new ICG fluorescent technique with a NIRF camera system is safe, enables live view of the results of the procedure, and does not create additional costs. However, it highlights more lymph nodes than the radioactive method.

Radio-Guided Lymph Node Mapping in Bladder Cancer Using SPECT/CT and Intraoperative γ-Probe Methods.

PURPOSE: Lymph outflow from bladder tumor differs between individuals, making the prediction of the metastatic landing sites difficult. A "blind" template of lymphadenectomy has been tested as a solution to this problem. We believe that it is feasible to find methods enabling more precise lymph nodes (LNs) evaluation. The aims of our study were to evaluate the possibility of LNs mapping in case of muscle invasive bladder cancer (MIBC) and to compare the 2 methods of their detection. PATIENTS AND METHODS: Our study group consisted of 38 cN0 MIBC patients. Lymph nodes mapping was performed by SPECT/CT lymphoscintigraphy using Tc-nanocolloid, followed by intraoperative verification with γ-ray probe. Lymph nodes with increased radiotracer uptake (hot spots) were removed, and then pelvic LNs dissection was conducted. Lymph nodes resected as hot spots and LNs resected with lymphadenectomy were separately examined by a pathologist. RESULTS: An average of 3 hot spots (range, 1-5) were identified in each case. For 36 of 38 patients, both preoperative SPECT/CT and intraoperative γ-probe evaluation results were obtained. Ninety-five percent of hot spots were found distally and caudally to the uretero-iliac crossing; 5% were found proximal. Lymph nodes outside the pelvic LNs dissection area did not contain metastases. In 2 patients, metastases were found in LNs without increased radiotracer uptake, and the observed hot spots contained no metastases. CONCLUSIONS: Radio-guided LNs mapping in case of MIBC is feasible. Preoperative detection of hot spots using SPECT/CT and intraoperative γ-ray detection probe gives similar results.

Comparison of Real-Time Fluorescent Indocyanine Green and (99m)Tc-Nanocolloid Radiotracer Navigation in Sentinel Lymph Node Biopsy of Penile Cancer.

INTRODUCTION: The aim of this study was to compare lymphatic drainage patterns detected with fluorescent dye indocyanine green (ICG) with the lymphatic drainage patterns detected with radiotracer (99m)Tc-nanocolloid in dynamic sentinel node biopsy (DSNB) procedures. PATIENTS AND METHODS: Fourteen patients with penile cancer and no palpable lymph nodes were included prospectively for DSNB. First, on the day of surgery (99m)Tc-nanocolloid was injected at the lesion site. Then, single photon emission computed tomography (SPECT) lymphoscintigraphy was performed. ICG was injected in the same manner as the radiotracer just before the surgery. In all cases partial penectomy and DSNB were performed. Sentinel lymph nodes (SLNs) were localized intraoperatively using the gamma-ray detection probe for radiocolloid and near infrared fluorescence (NIRF) camera for ICG. RESULTS: Transcutaneously, lymphatic nodes were identified in all 14 patients using the gamma probe and in 10 patients using the NIRF camera. After skin incision, fluorescent nodes were observed using the NIRF camera in the remaining 4 patients. The examination led to identification of 32 SLNs in total using technetium and ICG and additionally 3 more nodes visible only using ICG. All SLNs found using SPECT were also fluorescent. In 3 patients ICG enabled only approximate localization of the SLNs. Of 35 SLNs, 30 were negative and 4 were positive for metastasis. CONCLUSION: Our analysis of the effectiveness of ICG compared with radiocolloid in the DSNB for penile cancer indicates that they are comparable with some specific advantages and disadvantages. These findings must be studied further in a larger group of patients.

Nuclear imaging of amyloidosis.

Summary Amyloidosis is a clinical condition caused by deposition of various protein fibrills in extracellular space. The presented symptoms depend on the type of deposits and the organ or organs involved. The correct diagnosis is often difficult, due to lack of nonivasive imaging techniques and insufficiency of morphological imaging procedures delievered by radiology. We presented a list of potential radiopharmaceuticals that can be used in detecting various types of amyloidoses. (123)I-SAP proved to have high sensitivity in imaging of AA and AL amyloidosis in visceral organs. (99m)Tc-Aprotinin was found to be useful in detecting cardiac amyloidosis. A couple of classical radiotracers, such as (201)Tl, (123)I-mIBG, together with (111)In-antimyosin were also tested for accuracy in cardiac imaging, however the main problem was low specificity. Potential applicability was also found in case of some bone-seeking agents and other radiotracers, e.g. (67)Ga-citrate and (99m)Tc-penta-DMSA. High sensitivity and specificity was achieved with ß2-microglobulin labeled with (131)I or (111)In. Among PET tracers, (11)C-PIB deserves more attention, because it may have an important role in diagnosing of AD in the near future. Further clinical studies are expected to take place, because noninvasive diagnosing and monitoring of amyloidosis is still a challenge.

Preoperative detection of sentinel lymph nodes in endometrial cancer using SPECT/CT.

We report the use of SPECT/CT in sentinel lymph node biopsy in endometrial cancer. The patient was a 54-year-old woman with the diagnosis of endometrial adnenocarcinoma, grade 2. Preoperative MRI and transvaginal ultrasound scans revealed tumor infiltrating more than 50% of the myometrium. The patient was qualified for total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic/paraaortic lymphadenectomy. Before the surgery, 2 cervical injections of the (99m)Tc-labeled nanocolloid (0.5 mCi) were administered and the SPECT/CT was performed using a standard dual-head gamma camera and a 6-slice spiral CT component.

Comparison of SPECT-CT results and intraoperative detection of sentinel lymph nodes in endometrial cancer.

OBJECTIVES: The aim of the study was to compare the results of single-photon emission computed tomography-computed tomography (SPECT-CT) with those of intraoperative gamma probe detection and assess the clinical utility of SPECT-CT for sentinel lymph node biopsy in endometrial cancer. MATERIALS AND METHODS: We investigated 70 patients with endometrial cancer who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node biopsy (routine pelvic and para-aortic lymphadenectomy was additionally performed in high-risk patients). Tc-99m radiocolloid albumin was injected into the cervix and a blue dye was injected superficially into the fundus. RESULTS: SPECT-CT revealed hot spots in 64 patients (91.4%). The detection rates were 97.1 and 94.3% using the combined technique and the hand-held gamma probe, respectively. In 19 cases (27.1%) 35 hot spots detected on SPECT-CT were not diagnosed as sentinel lymph nodes (SLNs) during surgery. In each patient with undetected hot spots located in the common iliac or para-aortic regions, hot SLNs were found during surgery in the obturator or external iliac region. In addition, SPECT-CT had detected 88.9% of the SLNs found during surgery. With respect to the 13 cases not detected on SPECT-CT, the hot SLNs had very low activity. Using the combined method, 95.1% of SLNs were found in typical locations (external iliac or obturator nodes). There were two metastatic nodes: one in SLN and one in nonsentinel node. CONCLUSION: SPECT-CT yields a high SLN detection rate; however, there is significant discrepancy in comparison with intraoperative findings, which limits its clinical utility. In addition, in the majority of cases SLNs are found in typical areas, which means that they can be reliably detected using an intraoperative gamma probe.

Advantages of hybrid SPECT-CT imaging in preoperative localization of parathyroid glands in a patient with secondary hyperparathyroidism. A case report.

BACKGROUND: Secondary hyperparathyroidism is a frequent complication of chronic renal failure. Patients resistant to pharmacotherapy are candidates for parathyroidectomy. Invasiveness of surgical treatment can be minimized by precise preoperative localization of parathyroid glands. Imaging modalities routinely used for this purpose are ultrasonography and MIBI-Tc99m scintigraphy. CASE REPORT: Our case report shows advantages of co-registered computer tomography and conventional SPECT imaging (SPECT/CT) in a patient with advanced secondary hyperparathyroidism successfully treated with surgery. RESULTS: Hybrid SPECT/CT parathyroid imaging enables better surgical planning and is superior to conventional scintigraphy.

Sentinel lymph node detection with the use of SPECT-CT in endometrial cancer--analysis of two cases.

On the basis of two cases we discuss the important issues regarding the sentinel lymph node detection biopsy (SLNB) in endometrial cancer with combined cervical administration of the radiocolloid and the subserosal blue dye injection. The first patient (endometrioid adenocarcinoma G2, invasion > 50% myometrium) had 4 SLNs detected. Three were both hot and blue (detected on SPECT-CT). The fourth, paraaortic SLN was blue only. None of the lymph nodes contained metatstases. The second patient (endometrioid adenocarcinoma G1, invasion > 50% myometrium) had 4 SLNs detected. Three were blue (but two of them had also very low radioactivity). The fourth SLN was hot only. Blue only node contained macrometastasis. In the past patients underwent cervical amputation. Diverse distribution of each tracer confirms the advantages of the combined tracers administration in SLNB. The radiotracer is the crucial component--uptake was present in 6 of 8 SLNs. Although the blue dye is more a complimentary method, its suberosal injection significantly increases the safety of the SLNB procedure. In the first case we have detected blue only SLN in paraaortic region which otherwise would be missed using the cervical approach only. More importantly in the second case the tracer uptake was very limited due to the previous surgery and the blue dye administration allowed correct SLNs detection (including the metastatic node). Presented clinical cases confirms that the combined cervical and subserosal tracers administration together with preoperative SPECT-CT constitute an optimal SLN detection method and correctly provides information about the regional lymph node status.