Table 2.
Clinical studies of 99mTc-HYNIC-Annexin A5 in oncology.
| Reference | Patients (n) | Imaging time-points | Aim of the study | End points | Results |
|---|---|---|---|---|---|
| Van de Wiele et al. 2003 [56] | HNC (18) | Baseline | Identifying the relationship between baseline quantitative 99mTc-HYNIC-Annexin A5 tumor uptake and the number of apoptotic cells derived from histologic analysis after surgical resection. | n.a. | Quantitative 99mTc-HYNIC-Annexin A5 tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered. |
| Vermeersch, Ham et al. 2004 [58] | HNC (11) | Baseline | Estimation of the intra-, inter-, and day-to-day reproducibility of quantitative 99mTc-HYNIC-Annexin A5 tumor uptake values. | n.a. | The mean differences for the intra-, inter-. and day-to-day measurements were −3.4%, 2.4%, and −6%, respectively. |
| Vermeersch, Loose et al. 2004 [59] | HNC (18) | Baseline | 99mTc-HYNIC-Annexin A5 visualization of primary HNC lesions and lymph nodes before surgical resection and lymph node dissection. | n.a. | 99mTc-HYNIC-Annexin A5 allowed for the visualization of all primary HNC tumors identified by CT scan, but failed to identify most of the sites of lymph node involvement. |
| Haas et al. 2004 [66] | FL (11) | Baseline + up to 48 h ASOT | Evaluation of 99mTc-HYNIC-Annexin A5 imaging for monitoring radiation-induced apoptotic cell death. | n.a. | In 10 patients, post-treatment cytology matched 99mTc-HYNIC-Annexin A5 uptake ASOT. Baseline uptake was weak or absent. |
| Kartachova et al. 2004 [67] | FL (22) NSCLC (5) HNC (2) |
Baseline + up to 72 h ASOT | Predicting outcome of various treatments by 99mTc-HYNIC-Annexin A5 imaging. | TRR | Only patients with a CR or PR showed a significant increase in 99mTc-HYNIC-Annexin A5 uptake ASOT. |
| Rottey et al. 2006 [71] | M (3) Bl (1) BrC (5) HNC (2) Other (6) |
Baseline + 5–7 and 40–44 h ASOT | Predicting outcome of chemotherapy by 99mTc-HYNIC-Annexin A5 imaging. | TRR | 99mTc-HYNIC-Annexin A5 imaging allowed for separation of responders and non-responders to treatment in 16 of the 17 patients. |
| Rottey et al. 2007 [60] | HNC (8) BrC (6) M (2) Other (7) |
Baseline | Predicting outcome of (radio)chemotherapy by baseline uptake of 99mTc-HYNIC-Annexin. | TRR | Significantly higher pre-treatment tracer uptake was found in therapy responders (CR, PR) compared to non-responders (PD, SD). |
| Kartachova et al. 2007 [68] | NSCLC (14) | Baseline + up to 48 h ASOT | Predicting outcome of platinum-based chemotherapy by 99mTc-HYNIC-Annexin A5 imaging. | TRR | Patients with notably increased 99mTc-HYNIC-Annexin A5 uptake showed CR or PR. SD or PD showed less prominently increased or decreased tracer uptake. |
| Kartachova et al. 2008 [69] | NSCLC (4) HNC (3) FL (26) |
Baseline + 24–48 h ASOT | Identifying the reliability of visual analysis of 99mTc-HYNIC-Annexin A5 tumor uptake compared to quantitative tracer uptake evaluation. | TRR | Both visual (r = 0.97, p < 0.0001) and quantitative (r = 0.99, p < 0.0001) analysis of 99mTc-HYNIC-Annexin A5 tumor uptake significantly correlated with TRR. |
| Hoebers et al. 2008 [70] | HNC (13) | Baseline + up to 24 h ASOT | Predicting outcome of cisplatin-based chemoradiation by 99mTc-HYNIC-Annexin A5 imaging. | TRR DFS OS | 99mTc-HYNIC-Annexin A5 imaging showed a radiation-dose-dependent uptake in parotid glands. No correlation could be established between baseline or treatment induced tracer uptake and TRR, DFS or OS. |
| Loose et al. 2008 [61] | HNC (29) | Baseline | Identifying prognostic value of baseline 99mTc-HYNIC-Annexin A5 imaging. | DFS OS | 99mTc-HYNIC-Annexin A5 pre-treatment uptake was inversely correlated with DFS and OS. |
| Rottey et al. 2009 [72] | HNC (4) BrC (2) Other (5) |
2× Baseline within 40–44 h from each other or baseline + 5–7 and 40–44 h ASOT | Determining the influence of chemotherapy on the biodistribution of 99mTc-HYNIC-Annexin in healthy tissues. | n.a. | No significant differences in 99mTc-HYNIC-Annexin uptake in healthy tissues were found between patients which received chemotherapy and which did not. |
HNC, head and neck cancer; CT, computed tomography; DFS, disease free survival; OS, overall survival; TRR, tumor response rate; ASOT, after start of therapy; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; FL, follicular lymphoma; NSCLC, non-small cell lung cancer; M, melanoma; Bl, bladder; BrC, breast cancer; n.a., not applicable.