68Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with 18F-FDG

Abstract

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of ⁶⁸Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with ¹⁸F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of ⁶⁸Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with ⁶⁸Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUV_max was significantly higher on ⁶⁸Ga-FAP-2286 PET than on ¹⁸F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: ⁶⁸Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,⁶⁸Ga-FAP-2286 PET had consistently higher uptake than ¹⁸F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.

Keywords: FAP-2286; PET; dosimetry; fibroblast activation protein.

Graphical abstract

FIGURE 1.

Tumor uptake by tumor type. SUV_max-avg represents average SUV_max of hottest lesion per patient. Error bars represent 95% CI. Average blood pool uptake (BP) was 1.4.

FIGURE 2.

Comparison of paired SUV_max across various cancer types imaged with ⁶⁸Ga-FAP-2286 PET vs. ¹⁸F-FDG PET. Error bars represent 95% CI. *P < 0.05.

FIGURE 3.

A 58-y-old man with newly diagnosed nasopharyngeal carcinoma. (A) Maximum-intensity projections, axial fused PET, and axial PET images from ¹⁸F-FDG PET/CT demonstrate known nasopharyngeal mass with SUV_max of 23.7 (solid arrow), along with small but mildly hypermetabolic left cervical and axillary lymph nodes with SUV_max of up to 3.7 (dashed arrows, dotted circle). (B) Maximum-intensity projections, axial fused PET, and axial PET images from ⁶⁸Ga-FAP-2286 PET/CT demonstrate only nasopharyngeal mass with SUV_max of 12.7 (arrow), with no uptake in the cervical lymph nodes (dotted circle). Fine-needle aspiration of left cervical node revealed reactive changes, which was attributed to recent coronavirus disease 2019 vaccine.

FIGURE 4.

A 72-y-old woman with metastatic invasive lobular breast cancer. ⁶⁸Ga-FAP-2286 PET (A) revealed extensive metastatic disease not seen on ¹⁸F-FDG PET (B), including small mediastinal and hilar lymph nodes (A, solid black arrow), diffuse gastric mucosal disease (A, dotted black arrow), and extensive peritoneal disease (SUV_max, 7.1; A, black arrowhead and white arrow). Uptake seen on ¹⁸F-FDG PET in abdomen reflects physiologic uptake in bowel (B, black arrowhead) rather than tumor.

FIGURE 5.

A 69-y-old man with cholangiocarcinoma imaged using PET/MRI. (A) ⁶⁸Ga-FAP-2286 images demonstrate uptake within hepatic metastases. Uptake is more central (solid arrow), which correlates with region of delayed enhancement on MRI (dashed arrow). (B) ¹⁸F-FDG PET/CT demonstrates more peripheral uptake associated with more cellular component of tumor (arrow).