Molecular imaging in oncology: Common PET/CT radiopharmaceuticals and applications

Abstract

PET/CT is a commonly used modality in cancer imaging, as it can help in diagnosis, staging and assessment of treatment response in many cancer types. A better understanding of the tumor microenvironment and identification of multiple selective targets are promoting further investigation into different radiotracers for diagnosis and therapy. In the past few decades many radiopharmaceuticals have emerged for specific oncologic indications providing superior detection rate than some morphologic modalities. The purpose of this review is to provide an update on the most current radiopharmaceuticals used in cancer imaging including the mechanism of action, indications and pitfalls.

Keywords: Oncology; PET/CT (Positron Emission Tomography/Computed Tomography); Radiopharmaceutical; Radiotracers.

Fig. 1

Detection of metastasis on ¹⁸F-FDG PET/CT not otherwise seen on CT. 63-year-old woman presenting with left upper lobe mass. (A) Maximum-intensity-projection image (MIP) shows intense ¹⁸F-FDG uptake in the left upper lobe (solid arrow) and mediastinal nodes (dashed arrow) as well as focal liver uptake and uptake in the left shoulder. Axial fused PET/CT and CT images of the upper abdomen (B) and upper chest (C) show ¹⁸F-FDG-avid hepatic lesion (white arrow) and multiple osseous lesions in the left scapula (blue arrows) and thoracic vertebral body, which were not visualized on CT.

Fig. 2

Evaluation of Lymphoma with ¹⁸F-FDG PET/CT. 43-year-old woman with recent diagnosis of Hodgkin’s Lymphoma, nodular sclerosis subtype. Baseline ¹⁸F-FDG PET/CT is shown. (A) Maximum-intensity-projection image (MIP), axial PET, fused PET/CT and CT (B) through the upper chest and (C) upper abdomen. Multistation intensely ¹⁸F-FDG-avid lymph nodes in the left axilla (dashed arrow), mediastinum (solid arrow) and retroperitoneum (blue arrow), as well as multiple ¹⁸F-FDG-avid foci of uptake in the spleen without CT correlate in non-enhanced CT (asterisk). Diffuse bone marrow uptake in the axial and appendicular skeleton is better appreciated in the MIP images, may indicate bone marrow involvement in the absence of ongoing treatment or be reactive to systemic process (bone marrow biopsy is needed). Physiologic uptake in the liver, brain, bowel, kidneys and breast tissue.

Fig. 3

Metabolic pattern of ¹⁸F-FDG suggesting transformation to high-grade lymphoma. 49-year-old woman with recently diagnosed stage I-II follicular lymphoma on an excisional biopsy of a left axillary lymph node. Patient presented with new acute onset abdominal pain and underwent evaluation with ¹⁸F-FDG PET/CT. (A and B) MIP and coronal fused PET/CT shows extensive ¹⁸F-FDG-avid disease including lymphadenopathy above and below the diaphragm and involvement of the liver, stomach, left kidney, bladder, uterus, multiple muscles and left clavicle involvement. High intensity of ¹⁸F-FDG uptake (SUVmax 22) is discordant with finding on pathology. ¹⁸F-FDG pattern of uptake is consistent with transformed follicular lymphoma to a high-grade lymphoma.

Fig. 4

Systemic evaluation of neuroendocrine tumors expressing somatostatin receptors. 71-year-old woman with SDHD mutation and multiple paragangliomas. (A) MIP image demonstrates increased ⁶⁸Ga-DOTATATE uptake at multiple soft tissue lesions. Axial PET, CT and fused PET/CT in the (B) skull base (right glomus vagale), (C) pericardial recess and (D) tail of the pancreas in the left upper quadrant consistent with paragangliomas expressing somatostatin receptors.

Fig. 5

Neuroendocrine tumor imaging and pitfalls. ⁶⁸Ga-DOTATATE PET/CT in a patient with metastatic neuroendocrine tumor. (A) MIP shows multiple foci of increased radiotracer uptake in lymph nodes of the mediastinum, left supraclavicular region, upper and lower abdomen as well as many hepatic metastases. Faint ⁶⁸Ga-DOTATATE uptake projecting in the left lower skull (solid arrow) corresponds to a partially calcified extra-axial lesion in the left posterior skull seen on fused PET/CT and CT (B and C). Subsequent MRI shows signal characteristics compatible with meningioma on T2 fat-sat and post-contrast T1 (D and E).

Fig. 6

Peritoneal carcinomatosis with ¹⁸F-FDG and ¹⁸F-FAPI-04 PET/CT. (Reprinted, with permission from Ref. [42]). (A) ¹⁸F-FDG PET maximum-intensity-projection image demonstrates focal uptake in the region of cecum and transverse colon and possible diffuse peritoneal disease. (B) Corresponding ¹⁸F-FAPI-04 PET maximum-intensity projection clearly demonstrates diffuse peritoneal disease including involvement of subphrenic spaces. These images were originally published in JNM. Rodney J. Hicks et al. J Nucl Med 2021;62:296–302 © SNMMI .

Fig. 7

Evaluation of gastric cancer with ¹⁸F-FAPI PET/CT. Gastric cancer with node, liver, and brain metastases. (A) ¹⁸F-FAPI PET maximum-intensity projection. (B) Necrotic left occipital metastasis on transaxial ¹⁸F-FAPI PET. (C) Correlative CT. Adapted. These images were originally published in JNM. Rodney J. Hicks et al. J Nucl Med 2021;62:296–302 © SNMMI

Fig. 8

¹⁸F-FES PET/CT in breast cancer. ¹⁸F-FES PET/CT and ¹⁸F-FDG PET/CT (performed one week prior) in an 85-year-old woman with newly diagnosed ER+ left breast invasive lobular carcinoma. (A) ¹⁸F-FES PET/CT MIP shows the primary lesion in the left breast (black arrowhead) with ipsilateral axillary lymphadenopathy (white arrowhead), right breast masses (white arrow) and multiple bone lesions (black arrows). Note the standard field of view for ¹⁸F-FES PET/CT includes the skull vertex for detection of additional bone metastases (black asterisk). Note physiologic biliary excretion of ¹⁸F-FES (white asterisk). (C-H) Representative axial fusion images show enhanced ¹⁸F-FES uptake in lesions compared to ¹⁸F-FDG using similar window level: (C) left axillary levels 1, 2, and 3 lymphadenopathy with SUVmax 32 on ¹⁸F-FES and (D) SUVmax 3.3 on ¹⁸F-FDG, (E) left third rib with SUVmax 4.3 with ¹⁸F-FES and (F) SUVmax 2.5 with ¹⁸F-FDG, and (H) right C5 pedicle with SUVmax 5 with ¹⁸F-FES without appreciable uptake above background with ¹⁸F-FDG (I). There is concordant uptake between ¹⁸F-FES and ¹⁸F-FDG PET/CT, more so with ¹⁸F-FES, suggesting a favorable response to hormone-directed therapies. Courtesy of Lacey McIntosh D.O., M.P.H. (University of Massachusetts Memorial Medical Center).

Fig. 9

69-year-old male with history of metastatic castration resistant prostate cancer with rising PSA on Cabazitaxel. Rising PSA levels, 4.98 ng/mL in September 2021 and 14.8 ng/mL in April 2022. (A) MIP ¹⁸F-DCFPyL PET/CT in October 2021 with multifocal PSMA-avid disease including uptake at the prostate bed (dashed arrows), pelvis nodes and bones of the axial and appendicular skeleton. (B) MIP PET/CT of ⁶⁸Ga-PSMA-11 (May 2022) shows similar extent of disease. (C) ⁶⁸Ga-PSMA-11 axial PET and fused PET/CT with focal uptake in the prostate gland at the right apex (dashed arrows). (D) ⁶⁸Ga-PSMA-11 axial PET and CT showing right pelvic PSMA-avid lymph node.

Fig. 10

Detection of subcentimeter active prostate disease with PSMA-based radiotracers. 79-year-old man with history of prostate cancer treated with prostatectomy, radiotherapy, and adjuvant androgen deprivation therapy (ADT) with biochemical recurrence and raising PSA levels, 2.02 ng/mL around the time of the scan. (A) MIP ¹⁸F-DCFPyL PET/CT and (B and C) axial PET, fused PET/CT and CT through the retroperitoneum show intense focal uptake in the right common iliac nodal station of the pelvis (dashed arrow). (B) 4 mm left para-aortic (blue arrow) and (C) 3 mm retro-aortic lymph nodes (white arrow) that would have not otherwise been detected on conventional imaging due to small size.

Fig. 11

Non-prostatic lesions with increased PSMA uptake. 71-year-old man with history of metastatic renal cell carcinoma and prostate cancer. (A) Axial CT and fused PET/CT in the upper chest shows increased focal PSMA uptake associated with lytic bone lesions in a right anterior rib (white arrow) and (B) faint lytic lesion in the right scapula (blue arrow), consistent with metastases from renal cell carcinoma.