Table 1.
Preliminary case-by-case diagnostic value of RGD-containing peptides and FDG.
| Tumor type | Purpose | Preferred agents | Supporting evidence | Opposing evidence | Reference |
|---|---|---|---|---|---|
| GBM | HGG vs. LGG | RGD | 68Ga-PRGD2: TBR 0.80–2.00 vs. 3.55–11.00, sensitivity 100% (8/8), specificity 100% (4/4) | (114) | |
| 18F-FDG: TBR 0.57–1.38 vs. 1.11–4.77; sensitivity 88% (7/8), specificity 75% (3/4) | |||||
| meningioma vs. HGG | RGD | 68Ga-NOTA-PRGD2: SUVmax 4.23 ± 2.48 vs. 1.57 ± 0.33, p = 0.0047 | (115) | ||
| 18F-FDG: SUVmax 5.38 ± 2.37 vs. 12.64 ± 1.91, p = 0.0537 | |||||
| HNSCC | diagnosis of lesions | RGD and FDG | 68Ga-NODAGA-RGD vs. 18F-FDG: both detected 100% of primary lesions, lymph nodes, distant metastases | (87) | |
| Thyroid cancer | diagnosis of radioiodine-refractory thyroid cancer | RGD | 68Ga-DOTA-RGD2: sensitivity 82.3%, specificity 100%, accuracy 86.4%, PPV 100%, NPV 62.5% | 68Ga-DOTA-RGD2: detect 123 lesions. 63.6% patients; 10.6% thyroid bed lesions; 82.9% nodal lesions; 6.5% skeletal lesions | (92) |
| 18F-FDG: sensitivity 82.3%, specificity 50%, accuracy 75%, PPV 84.8%, NPV 45.4% | 18F-FDG: detect 144 lesions, 75.0% patients; 8.3% thyroid bed lesions; 86.1% nodal lesions; 5.5% skeletal lesions | ||||
| radioiodine-refractory lesions vs. benign lesions | none | 18F-Alfatide: SUVmean 2.5 ± 0.9 vs. 2.8 ± 0.9, p = 0.576 | (91) | ||
| 18F-FDG: SUVmean 4.5 ± 1.6 vs. 3.3 ± 1.2, p = 0.133 | |||||
| radioiodine-refractory lesions vs. iodine-avid lesions | none | 18F-Alfatide: SUVmean p >0.05 | |||
| 18F-FDG: SUVmean p >0.05 | |||||
| lesions diameter >1.5 cm vs. <1.5 cm in differentiated thyroid cancer | RGD | 18F-Alfatide: SUVmean 3.1 ± 0.7 vs. 2.4 ± 0.8, p <0.05 | |||
| 18F-FDG: SUVmean p >0.05 | |||||
| lymph nodes diameter >1 cm vs. <1 cm in differentiated thyroid cancer | none |
18F-Alfatide: SUVmean p = 0.06; 18F-FDG: SUVmean p = 0.41 |
|||
| Lung cancer | malignancies vs. benign ones | undefined | 68Ga-NOTA-PRGD2: sensitivity 83.8%, specificity 91.3%, accuracy 85.7% (SUVmean = 1.3); sensitivity 80.9%, specificity 82.6%, accuracy 81.3% (SUVmax = 2.0) | 18F-FDG: sensitivity 86.8%, specificity 69.6%, accuracy 82.4% (SUVmean = 2.0); sensitivity 85.3%, specificity 69.6%, accuracy 81.3% (SUVmax = 3.0) | (100) |
| metastatic vs. non-metastatic lymph nodes | RGD | 68Ga-NOTA-PRGD2: SUVmax 1.93 ± 1.03 vs. 0.75 ± 0.75, p <0.05; PPV 90.0%, NPV 93.8% | (100) | ||
| 18F-FDG: SUVmax 3.91 ± 2.37 vs. 2.30 ± 2.31, p = 0.48; PPV 30.2%, NPV 90.5% | |||||
| 18F-FDG: sensitivity 75%, specificity 66.7% | |||||
| lung cancer vs. tuberculosis | RGD | 18F-Alfatide II: SUVmax 4.08 ± 1.51 vs. 2.63 ± 1.34, p = 0.0078 | (117) | ||
| 18F-FDG: SUVmax 12.04 ± 4.67 vs. 7.53 ± 2.88 | |||||
| NSCLC vs. SCLC | RGD | 68Ga-DOTA-RGD2: SUVmax 3.83 ± 1.00 vs. 2.05 ± 0.74, p <0.0001; TNR 1.94 ± 0.70 vs. 0.94 ± 0.24, p = 0.0099 | (111) | ||
| 18F-FDG: SUVmax 10.39 ± 4.03 vs. 7.84 ± 2.25, p = 0.08;TNR 5.03 ± 2.52 vs. 3.62 ± 0.93, p = 0.10 | |||||
| diagnosis of neuroendocrine tumor | RGD | 68Ga-NOTA-3P-TATE-RGD vs. 18F-FDG: 24.12 ± 22.39 vs. 3.75 ± 2.81, p = 0.0241 | (52) | ||
| ESCC | pathological stages I–II vs. III–IV | RGD and FDG | 18F-Alfatide: 2.41 ± 1.06 vs. 3.41 ± 0.68, p = 0.03 | ||
| 18F-FDG: 4.02 ± 1.83 vs. 7.24 ± 3.70, p = 0.002 | |||||
| positive vs. negative lymph nodes | RGD and FDG | 18F-Alfatide: 3.57 ± 0.58 vs. 2.16 ± 0.80, p = 0.001 | |||
| 18F-FDG: 7.41 ± 3.35 vs. 3.2 ± 0.44, p < 0.001 | (118) | ||||
| well vs. moderate vs. poor differentiation | RGD | 18F-Alfatide: 2.44 ± 0.83 vs. 2.91 ± 0.62 vs. 3.56 ± 0.98, p = 0.049 | |||
| 18F-FDG: 3.26 ± 0.36 vs. 4.49 ± 1.67 vs. 7.05 ± 4.02, p = 0.053 | |||||
| Breast cancer | diagnosis of breast and metastatic lesions | RGD | 18F-FPPRGD2: sensitivity, all lesions 95.7%, breast lesions 100%, axillary lymph nodes 75.0%, bone 100%, other metastases 100%; specificity, all lesions 100%, breast lesions 100%, axillary lymph nodes 100%, bone 100%, other metastases 100% | 18F-RGD-K5 detected only 122 lesions (77.7%) among 157 lesions observed on 18F-FDG PET | (98) |
| 18F-FDG: sensitivity, all lesions 87.0%, breast lesions 83.3%, axillary lymph nodes 75.0%, bone 87.5%, other metastases 100%; specificity, all lesions 57.1%, breast lesions 100%, axillary lymph nodes 0%, bone 100%, other metastases 0% | (63) | ||||
| breast cancer vs. benign breast lesion | undefined | 18F-Alfatide II: sensitivity 97.6% (SUVmax = 1.6); 18F-FDG: sensitivity 78.6% (SUVmax = 3.68) | 18F-Alfatide II: specificity 54.5%, Youden index 52.1%, AUC 0.738; 18F-FDG: specificity 81.8%, Youden index 60.4%, AUC 0.838 | (88) | |
| different HR status | RGD |
68Ga-BBN-RGD: ER(+) vs. ER (–), p = 0.0083 18F-Alfatide II: Luminal A/Luminal B vs. Triple negative, p = 0.032/0.026; 68Ga-NOTA-RGD: ER/PR(+),HER2(−) or ER/PR(+),HER2(+) vs. ER/PR(−),HER2(−), p <0.05 |
18F-FDG: ER/PR(+),HER2(−) or ER/PR(+),HER2(+) vs. ER/PR(−),HER2(−), p <0.05 | (116) | |
| different HER2 status | FDG | 18F-FDG: HER-2(+) vs. Luminal A/Luminal B, p = 0.001/0.000 68Ga-BBN-RGD: HER-2(+) vs. HER-2(−), p = 0.6589 | 68Ga-NOTA-RGD: HER2(+) vs. HER2(−), 2.90 ± 0.75 vs. 2.42 ± 0.59, p = 0.04 for SUVmax; 1.95 ± 0.53 vs. 1.60 ± 0.38, p = 0.04 for SUVmean | (89) | |
| HCC or liver metastasis | diagnosis | FDG | 68Ga-DOTA RGD: 0 patients; 18F-FDG: detect liver metastases in 9 patients (16%) | (119) | |
| LARC | diagnosis | FDG | 18F-FPRGD2: 18 (51%) pelvic lymph nodes; 18F-FDG: 35 pelvic lymph nodes | (66) | |
| Metastatic RCC | diagnosis | undefined | 18F-FPPRGD2: 55/60 lesions; 18F-FDG: 52/60 lesions | (97) | |
| Cervical cancer and ovarian cancer | diagnosis | undefined | 18F-FPPRGD2: 48/52 lesions; 18F-FDG: 50/52 lesions | (90) | |
| Brain metastasis | diagnosis | RGD | 18F-Alfatide II: detected 100% of lesions, TNR 18.9 ± 14.1; 18F-FDG: 50% of lesions, TNR 1.5 ± 0.5 | (47) | |
| Bone metastasis | diagnosis | undefined | 18F-Alfatide II: 100% of osteolytic metastases, 70% of osteoblastic metastases, 100% of mixed bone metastases, 98% of bone marrow metastases, 92% of all metastases | (120) | |
| 18F-FDG: 90% of osteolytic metastases, 53% of osteoblastic metastases, 90% of mixed bone metastases, 77% of bone marrow metastases, 77% of all metastases |
GBM, glioblastoma multiforme; HGG, high-grade glioma; LGG, low-grade glioma; TBR, tumor-to-blood ratio; SUVmax, maximum standard uptake values; HNSCC, squamous cell carcinoma of head and neck; PPV, positive predictive value; NPV, negative predictive value; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; TNR, tumor-to-normal ratio; ESCC, esophageal squamous cell carcinoma; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; HCC, hepatocellular carcinoma; LARC, locally advanced rectal cancer; RCC, Renal cell cancer.