Quarter-Century PET/CT Transformation of Oncology: Lymphoma.

The clinical landscape of lymphomas has changed dramatically over the last 2 decades, including significant progress made in the understanding and utilization of imaging modalities and the available treatment options for both indolent and aggressive lymphomas. Since the introduction of hybrid PET/CT scanners in 2001, the indications of 18F-fluorodeoxyglucose (FDG) PET/CT in the management of lymphomas have grown rapidly. In today's clinical practice, FDG PET/CT is used in successful management of the vast majority patients with lymphomas.

Aberrant Vascular Anatomy Associated With Artifactual Focal Avidity in the Liver on PSMA PET.

ABSTRACT: 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT is a valuable tool for staging and restaging of prostate cancer. Prostate-specific membrane antigen expression is not specific to prostate cancer, as it is expressed in normal tissues as well as in neoplastic and nonneoplastic processes. Awareness of the broad possibility of lesions with PSMA avidity is necessary to recognize normal variants and avoid potential pitfalls in image interpretation. We present a series of cases showing physiologic focal PSMA avidity in hepatic segment IVb. We correlate this uptake with aberrant hepatic vasculature. The awareness of this variant is important for accurate image interpretation to prevent additional invasive procedures, undue treatment escalation, and denial of curative treatment to patients.

FDG PET/CT-based Response Assessment in Malignancies.

Response is the logical outcome measure of a treatment in a clinical or research setting. Objective response assessment involves the use of a test to segregate patients who are likely to experience improved survival from those who are not. Early and accurate response assessment is critical for determining therapy effectiveness in clinical settings, for effective trial designs comparing two or more therapies, and for modulating treatment on the basis of response (ie, response-adapted therapy). 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) PET/CT can provide both functional and structural information about a disease process. It has been used at several stages of patient management, including imaging-based tumor response assessment, for various malignancies. FDG PET/CT can be used to differentiate patients with lymphoma who have a residual mass but no residual disease after treatment (ie, complete responders) from those who have a residual mass and residual disease after treatment. Similarly, in solid malignancies, the functional changes in glucose uptake and metabolism precede the structural changes (commonly seen as tumor shrinkage) and necrosis. Response assessment criteria have been developed on the basis of findings on FDG PET/CT images and are continuously being revised to ensure standardization and improve their predictive performance. Published under a CC BY 4.0 license. Quiz questions for this article are available through the Online Learning Center.

Comparison of positional artifacts in myocardial perfusion imaging in supine and semi-reclining position using dedicated D-SPECT cardiac camera: validation using CT based attenuation correction.

BACKGROUND: Soft-tissue attenuation remains a major limitation of SPECT-MPI which interferes with the diagnosis of CAD. The current study aims to evaluate the pattern of attenuation artifacts in supine and semi-reclining positions on CZT cardiac camera and their interaction with gender, BMI and stress protocols. METHODS: We prospectively analysed 150 patients acquired in supine and semi-reclining positions on CZT camera. The images were evaluated for severity and extent of defect using 17-segment model. An additional CT scan was acquired to generate AC image in the first 50 patients studied to assist investigator learning for comparison of artifact vs true defects in the two SPECT systems. The defects present in one position or showing change in severity within two positions were considered as positional artifacts and further validated using CTAC supine image. RESULTS: In overall analysis, higher extent and severity of positional artifacts were observed more in semi-reclining position affecting the apex, apico-inferior, inferolateral and inferoseptal segments. Females showed more positional artifacts than males with inferior wall attenuation in the semireclining position and anterior wall attenuation in the supine position. A positive correlation of the extent and severity of positional artifacts was noted with an increasing BMI. In patients with BMI > 30, mid inferior and inferolateral segments were most affected followed by anterior wall segments. Highest correction of artifactual perfusion defects by CTAC was noted in inferior wall followed by inferolateral segments. CONCLUSION: The incidence of positional artifacts was greater in semi-reclining position in females, higher BMI groups and adenosine stress subsets. Knowledge of the pattern of positional artifacts appears to be a reliable alternative of CTAC for correct interpretation of myocardial perfusion images.

Adverse Clinical Events at the Injection Site Are Exceedingly Rare After Reported Radiopharmaceutical Extravasation in Patients Undergoing 99mTc-MDP Whole-Body Bone Scintigraphy: A 12-Year Experience.

The deleterious effects of high-dose radiation on normal tissue are sometimes extrapolated to diagnostic (SPECT and PET) radiopharmaceutical extravasation (RPE). It has been hypothesized that diagnostic RPE can have gradually evolving local tissue injury and a potentially increased risk of local dermatologic or oncologic diseases over a longer period. However, data on clinical adverse events after diagnostic RPE are limited. Therefore, our primary aim was to study the occurrence of short-term and long-term clinical adverse events in patients who underwent 99mTc-methylene diphosphonate (99mTc-MDP) whole-body bone scintigraphy (WBBS) with reported RPE. Methods: The records of 99mTc-MDP WBBS performed from June 2010 to January 2022 were retrospectively examined for RPE documented in the scan reports. The clinical records of patients with a documented RPE were extensively reviewed for any related short-term adverse events (within 2 wk of the WBBS: local symptoms and care sought for local dermatologic or musculoskeletal issues) and long-term adverse events (until the last follow-up: local deleterious effects and related consults for dermatology, plastic surgery, oncology, or orthopedics). Results: Retrospective review of the records of 31,679 99mTc-MDP WBBS studies showed RPE documented in 118 (0.37%). Medical records were not retrievable for 22 patients, yielding a final cohort of 96 patients with reported RPE. The median follow-up was 18.9 mo (interquartile range, 7.8-45.7 mo). Short-term events were noted in 4 patients, of whom one was asymptomatic. Of the 3 symptomatic patients, 2 experienced mild discomfort at the injection site, and 1 had tender swelling. Three of the 4 events were in patients who had a prior intravenous contrast extravasation for contrast-enhanced CT performed earlier during the day and a 99mTc-MDP injection later at the same site, likely leading to RPE. None of the long-term local events had any plausible link with the RPE event. Conclusion: Reported RPE was rare, and 3 patients (0.009%) had short-term local symptoms, all of which were likely related to the prior higher-volume intravenous contrast extravasation. The smaller-volume diagnostic radiopharmaceutical injections for WBBS are highly unlikely to cause local symptoms on their own. No patient had any long-term adverse event with a plausible link to the RPE.

Diagnostic Accuracy of 99mTc-Sestamibi SPECT/CT for Characterization of Solid Renal Masses.

Our objective was to assess the diagnostic accuracy of 99mTc-sestamibi SPECT/CT for characterizing solid renal masses. Methods: Imaging and clinical records of patients who underwent 99mTc-sestamibi SPECT/CT for clinical work-up of their solid renal masses from September 2018 to October 2021 were retrospectively reviewed. Histopathology formed the reference standard, and the diagnoses were categorized as malignant/concerning (renal cell carcinomas [RCCs] other than chromophobe histology) and benign/nonconcerning (oncocytic tumors including chromophobe RCC, other benign diagnoses) to calculate the sensitivity and specificity of 99mTc-sestamibi SPECT/CT and contrast-enhanced CT (ceCT). The clinical reads of the SPECT/CT images were used for visual classification of the lesions. Additionally, the SPECT images were manually segmented to obtain the maximum and mean counts of the lesion and adjacent renal cortex and maximum and mean lesion Hounsfield units. Results: 99mTc-sestamibi SPECT/CT was performed on 42 patients with 62 renal masses. A histopathologic diagnosis was available for 27 patients (18 male, 9 female) with 36 solid renal masses. ceCT findings were available for 20 of these patients. The most commonly identified single histologic type was clear cell RCC (13/36; 36.1%). Oncocytic tumors were the most common group of nonconcerning lesions (15/36), with oncocytoma as the predominant histologic type (n = 6). The sensitivity and specificity of SPECT/CT for diagnosing a nonconcerning lesion were 66.7% and 89.5%, respectively, compared with 10% and 75%, respectively, for ceCT. The lesion-to-kidney ratios for maximum and mean counts and maximum lesion Hounsfield units showed significant differences between the 2 groups (P < 0.05). The lesion-to-kidney mean count ratio at a cutoff of 0.46 showed a sensitivity and specificity of 87.5% and 86.67%, respectively, for detecting nonconcerning lesions, which was significantly higher than that of ceCT. Conclusion: The current literature on the utility of 99mTc-sestamibi SPECT/CT for characterization of solid renal masses is limited. We offer additional evidence of the incremental value of 99mTc-sestamibi SPECT/CT over ceCT for differentiating malignant or aggressive renal tumors from benign or indolent ones, thereby potentially avoiding overtreatment and its associated complications. Quantitative assessment can further increase the diagnostic accuracy of SPECT/CT and may be used in conjunction with visual interpretation.

Mentorship in Nuclear Medicine-Why and How?

ABSTRACT: Mentorship is a highly gratifying relationship that requires commitment from all involved parties. Several different mentorship models exist that can be modified to suit the requirements of the mentors and mentees, and be fine-tuned for individuals at different career levels. Our proposed framework can be deployed as a pilot design for the trainees and early-career faculty members in nuclear medicine with the scope of appropriate timely modifications based on user feedback.

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer.

A 76-year-old man with metastatic castration-resistant prostate carcinoma progressing with antiandrogen and taxane therapy was treated with lutetium 177 prostate-specific membrane antigen (PSMA)-617 and showed marked biochemical and imaging response, with improvement in clinical status and osseous pain. A summary of nuclear medicine theranostics with emphasis on PSMA targeting agents is presented.

Molecular imaging phenotyping for selecting and monitoring radioligand therapy of neuroendocrine neoplasms.

Neuroendocrine neoplasia (NEN) is an umbrella term that includes a widely heterogeneous disease group including well-differentiated neuroendocrine tumours (NETs), and aggressive neuroendocrine carcinomas (NECs). The site of origin of the NENs is linked to the intrinsic tumour biology and is predictive of the disease course. It is understood that NENs demonstrate significant biologic heterogeneity which ultimately translates to widely varying clinical presentations, disease course and prognosis. Thus, significant emphasis is laid on the pre-therapy evaluation of markers that can help predict tumour behavior and dynamically monitors the response during and after treatment. Most well-differentiated NENs express somatostatin receptors (SSTRs) which make them appropriate for peptide receptor radionuclide therapy (PRRT). However, the treatment outcomes of PRRT depend heavily on the adequacy of patient selection by molecular imaging phenotyping not only utilizing pre-treatment SSTR PET but 18F-Fluorodeoxyglucose (18F-FDG) PET to provide insights into the intra- or inter-tumoural heterogeneity of the metastatic disease. Molecular imaging phenotyping may go beyond patient selection and provide useful information during and post-treatment for monitoring of temporal heterogeneity of the disease and dynamically risk-stratify patients. In addition, advances in the understanding of genomic-phenotypic classifications of pheochromocytomas and paragangliomas led to an archetypical example in precision medicine by utilizing molecular imaging phenotyping to guide radioligand therapy. Novel non-SSTR based peptide receptors have also been explored diagnostically and therapeutically to overcome the tumour heterogeneity. In this paper, we review the current molecular imaging modalities that are being utilized for the characterization of the NENs with special emphasis on their role in patient selection for radioligand therapy.

Detection of Additional Primary Neoplasms on 18F-Fluciclovine PET/CT in Patients with Primary Prostate Cancer.

The aim of this study was to evaluate the detection rate of incidental second primary neoplasms in patients with prostate cancer on 18F-fluciclovine PET/CT. Methods: Imaging reports and patient demographic data were retrospectively reviewed from 663 clinical 18F-fluciclovine PET/CT studies, performed in 601 patients for the assessment of their prostate cancer (643 - recurrence evaluation, 20 - initial staging) from August 2016 to April 2021. Maximum SUV (SUVmax) of the suspected second neoplasms was determined. The results of 18F-fluciclovine PET/CT were correlated with clinical and radiologic studies to determine the nature of the suspected second neoplasms. Results: Fifty-five patients (9.1%) had findings suggestive of a second neoplasm. Thirty-nine of 55 had a known second neoplasm diagnosed before the PET/CT. An incidental second primary neoplasm was first suspected on 18F-fluciclovine PET/CT in 16 of 601 patients (2.7%). Three of the 16 patients had PET/CT suggestive of a meningioma that was corroborated on MRI. Of the remaining 13 patients, 11 had a tissue diagnosis confirming a malignancy. Second malignancies included renal cell carcinoma (RCC; 5/11; 45.5%), urothelial carcinoma (n = 2), multiple myeloma, chondrosarcoma, cutaneous squamous cell carcinoma, and squamous cell carcinoma of the esophagus and lung (n = 1, each; except for 1 patient with both esophageal and lung carcinomas). Among histopathologically confirmed malignancies, clear-cell RCC had the lowest uptake (SUVmax 3.4), and cutaneous squamous cell carcinoma had the highest uptake (SUVmax 13.6). Of the 2 patients with no histopathologic confirmation, 1 had ultrasound and MRI findings corroborating the diagnosis of RCC. The other patient had a solitary lung nodule suggestive of primary lung carcinoma and elected to undergo observation. Conclusion: Incidental findings consistent with a second primary neoplasm are not infrequently seen on 18F-fluciclovine PET/CT performed for assessment of prostate cancer (9.1%). Of the incidentally detected primary cancers, RCC was the most common (45.5%). These findings indicate the need for a careful analysis of 18F-fluciclovine PET/CT images, due to the broad tumor imaging capabilities of this radiotracer.

Nephrotoxicity after radionuclide therapies.

Radioligand therapies have opened new treatment avenues for cancer patients. They offer precise tumor targeting with a favorable efficacy-to-toxicity profile. Specifically, the kidneys, once regarded as the critical organ for radiation toxicity, also show excellent tolerance to radiation doses as high as 50-60 Gy in selected cases. However, the number of nephrons that form the structural and functional units of the kidney is determined before birth and is fixed. Thus, loss of nephrons secondary to any injury may lead to an irreversible decline in renal function over time. Our primary understanding of radiation-induced nephropathy is derived from the effects of external beam radiation on the renal tissue. With the growing adoption of radionuclide therapies, considerable evidence has been gained with regard to the occurrence of renal toxicity and its associated risk factors. In this review, we discuss the radionuclide therapies associated with the risk of nephrotoxicity, the present understanding of the factors and mechanisms that contribute to renal injury, and the current and potential methods for preventing, identifying, and managing nephrotoxicity, specifically acute onset nephropathies.

Somatostatin Receptor Imaging and Theranostics: Current Practice and Future Prospects.

A new era of precision diagnostics and therapy for patients with neuroendocrine neoplasms began with the approval of somatostatin receptor (SSTR) radiopharmaceuticals for PET imaging followed by peptide receptor radionuclide therapy (PRRT). With the transition from SSTR-based γ-scintigraphy to PET, the higher sensitivity of the latter raised questions regarding the direct application of the planar scintigraphy-based Krenning score for PRRT eligibility. Also, to date, the role of SSTR PET in response assessment and predicting outcome remains under evaluation. In this comprehensive review article, we discuss the current role of SSTR PET in all aspects of neuroendocrine neoplasms, including its relation to conventional imaging, selection of patients for PRRT, and the current understanding of SSTR PET-based response assessment. We also provide a standardized reporting template for SSTR PET with a brief discussion.

Hyperphosphatemic Tumoral Calcinosis: A Classical Clinico-Radio-Scintigraphic Presentation.

Tumoral calcinosis is a rare entity presenting with periarticular calcium deposits, leading to multiple swellings and biochemical hyperphosphatemia and normocalcemia. Skeletal scintigraphy in these cases is helpful by providing a whole-body survey and delineating the common multifocality of this entity. We present the case of a 16-year-old boy with multiple swellings around the knee and elbow joints, having developed over 4 years and diagnosed as tumor calcinosis.

Response to Concomitant Enzalutamide and 177Lu-PSMA-617 Radioligand Therapy in ATM-Mutated Metastatic Castration Resistant Prostate Cancer.

ABSTRACT: Radioligand therapy with 177Lu-PSMA-617 has emerged as a promising treatment modality for patients with mCRPC (metastatic castration resistant prostate cancer). However, genomic defects in DNA damage repair mechanisms have been proposed to affect the radiosensitivity of prostate cancers. Patients harboring such deleterious mutations are, thus, unlikely to respond to 177Lu-PSMA-617 alone and would need a more tailored therapeutic approach. We report the case of a 68-year-old man with ATM mutation-positive mCRPC who showed exceptional response to concomitant administration of enzalutamide with 177Lu-PSMA-617.

Orbital and brain metastases on 68Ga-PSMA PET/CT in a patient with prostate carcinoma refractory to 177Lu-PSMA and 225Ac-PSMA therapy.

We present a case of metastatic prostate cancer with rare metastases involving the brain and orbit, in addition to liver, skeletal and nodal metastases. The patient had undergone prior hormonal therapy and chemotherapy and had disease progression despite 2 cycles of 177Lu-Prostate specific membrane antigen (177Lu-PSMA) based radioligand therapy. He had a partial response after 2 cycles of 225Ac-PSMA based targeted alpha therapy, as demonstrated on the 68Ga-PSMA PET/CT study. However, the patient had disease progression at the end of 4 cycles of 225Ac-PSMA therapy, evident by rising prostate specific antigen levels and imaging findings. The end of treatment 68Ga-PSMA PET/CT showed additional sites of metastases in the orbit and brain apart from overall disease progression. These are rare sites of distant spread in prostate cancer and require urgent evaluation and local treatment to prevent potential complications. The importance of detection of metastatic sites in closed cavities is because of the requirement for urgent intervention to avoid compression related complications.

Comparison of the diagnostic utility of 99mTc-PSMA scintigraphy versus 68Ga-PSMA-11 PET/CT in the detection of metastatic prostate cancer and dosimetry analysis: a gamma-camera-based alternate prostate-specific membrane antigen imaging modality.

OBJECTIVE: The present study was performed for head-to-head comparison between 68Ga-prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) and 99mTc-PSMA whole-body and regional single-photon emission computed tomography (SPECT)/CT for the detection of prostate cancer metastases. METHODS: Ten patients with metastatic prostate cancer underwent 99mTc-PSMA whole-body scan after intravenous injection of 230-330 MBq 99mTc-PSMA. Anterior and posterior whole-body images were acquired at 10 min, 2, 4 and/or 5/6 h post-injection. Additional SPECT/CT images were acquired for the involved sites, where planar images did not clearly identify the metastatic sites. All patients also underwent whole-body 68Ga-PSMA PET/CT and the results between the two techniques were compared for the detection of the metastatic lesions. Dosimetry analysis of the 99mTc-PSMA studies was performed using the MIRD-OLINDA approach. RESULTS: 68Ga-PSMA PET/CT detected lesions in all 10 patients, whereas 99mTc-PSMA imaging detected lesions in 9/10 patients. 68Ga-PSMA PET/CT imaging identified a total of 112 PSMA avid metastatic lesions compared to 57 (51%) lesions on 99mTc-PSMA imaging. Eighteen out of 57 lesions were detected only on delayed 99mTc-PSMA imaging at 4 h and/or 6 h. The regional 99mTc-PSMA SPECT detected 51/83 (61.0%) lesions seen on 68Ga-PSMA PET/CT. The dosimetry results demonstrated that 99mTc-PSMA provided organs' radiation absorbed/effective doses comparable with 99mTc-PSMA imaging. CONCLUSION: Whole-body 99mTc-PSMA combined with regional SPECT/CT could be a potential alternative to 68Ga-PSMA PET for the detection of the advanced stage metastatic prostate cancer and for response evaluation to PSMA-based targeted therapies.

Hepato-cardiac juxtaposition secondary to right hemi-diaphragmatic eventration on 99mTc-Sestamibi myocardial perfusion scintigraphy.

Liver radiotracer activity interfering with the inferior myocardial wall in a patient undergoing myocardial perfusion imaging (MPI) with 99mTc-Sestamibi is a known pitfall. We report a patient with pituitary macroadenoma who was subjected to stress-MPI study for pre-anesthetic clearance. The post-stress raw image showed the liver radiotracer activity in close approximation to the anteroseptal wall of the left ventricular myocardium, secondary to right hemi-diaphragmatic eventration.