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Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1-5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr(3)-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of (68)Ga-DOTA-iodo-Tyr(3)-octreotate [(68)Ga-DOTA,3-iodo-Tyr(3),Thr(8)]octreotide ((68)Ga-HA-DOTATATE; HA, high-affinity) compared to the established (68)Ga-DOTA-Tyr(3)-octreotate ((68)Ga-DOTATATE) in vivo.The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both (68)Ga-HA-DOTATATE and (68)Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner.(68)Ga-HA-DOTATATE and (68)Ga-DOTATATE showed comparable uptake in the liver (SUVmean 8.9 ± 2.2 vs. 9.3 ± 2.5, n.s.), renal cortex (SUVmean 13.3 ± 3.9 vs. 14.5 ± 3.7, n.s.) and spleen (SUVmean 24.0 ± 6.7 vs. 22.9 ± 7.3, n.s.). A somewhat higher pituitary uptake was found with (68)Ga-HA-DOTATATE (SUVmean 6.3 ± 1.8 vs. 5.4 ± 2.1, p 0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. (68)Ga-HA-DOTATATE demonstrated 328 lesions (95.3% of total lesions seen), and (68)Ga-DOTATATE demonstrated 332 lesions (96.4%). The mean SUVmax of all lesions was not significantly different between (68)Ga-HA-DOTATATE and (68)Ga-DOTATATE (17.8 ± 11.4 vs. 16.7 ± 10.7, n.s.).Our analysis demonstrated very good concordance between (68)Ga-HA-DOTATATE and (68)Ga-DOTATATE PET data. As the availability and use of (68)Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other (68)Ga-labelled hsst analogues.

Since the introduction of somatostatin receptor (sst) imaging using I-Tyr-octreotide [1], peptide receptor imaging and radiotherapy (PRRT) has become an established modality in the management of neuroendocrine tumours (NET) [2]. Based on the findings of a previous study [3] investigating metal-labelled DOTA-octreotides substituted at Tyr, we hypothesized that derivatives of DOTA-iodo-Tyr-octreotide might be excellent candidates for sstr imaging and therapy. Consequently, we evaluated Ga-DOTA-iodoTyr-octreo tate (Ga-HA-DOTATATE; HA, high affinity) in vitro and in a preliminary PET study. As hypothesized, Ga-HADOTATATE showed high affinity for human sst2,5 as well as diagnostic and logistical advantages, i.e. unlimited precursor availability. The (Leu,D-Trp, [I]Tyr)-SST28 IC50 values (in nanomoles) for Ga-HA-DOTATATE were >10.000 (sst1), 0.64±0.23 (sst2), >1,000 (sst3 and sst4) and 59.7±15.1 (sst5), and for Ga-DOTATATE were >10,000 (sst1), 0.67±0.25 (sst2), >1.000 (sst3), 822±327 (sst4) and >1,000 (sst5). In a first PET study a 73-year-old patient suffering from a NETwith unknown primary and liver metastases was investigated with Ga-HA-DOTATATE and Ga-DOTATATE. Both agents showed a possible small primary tumour in the midgut and five liver metastases that showed somewhat higher Ga-HA-DOTATATE uptake (mean SUVmax 23.8 vs. 21.6). The visual detectability of three small liver metastases with low uptake was superior with Ga-HADOTATATE. In summary, Ga-HA-DOTATATE provides high-quality images comparable to or better than those with GaDOTATATE. Further clinical studies are needed to confirm these first results and explore the use of HA-DOTATATE agents for PRRT.

Prostate cancer (PCA) is the second most common tumour in men worldwide. Whereas prostate specific antigen (PSA) is an established biochemical marker, the optimal imaging method for all clinical scenarios has not yet been found. With the rising number of PET centres there is an increasing availability and use of (18)F-/(11)C-choline or (11)C-acetate for staging of PCA. However, to date no final conclusion has been reached as to whether acetate or choline tracers should be preferred. In this review we provide an overview of the performance of choline and acetate PET for staging the primary and recurrent disease and lymph nodes in PCA, based on the literature of the last 10 years. Although predominantly choline has been used rather than acetate, both tracers performed in a similar manner in published studies. Choline as well as acetate have insufficient diagnostic accuracy for the staging of the primary tumour, due to a minimum detectable tumour size of 5 mm and inability to differentiate PCA from benign prostate hyperplasia, chronic prostatitis and high-grade intraepithelial neoplasia. Regarding lymph node staging, choline tracers have demonstrated a high specificity. Unfortunately, the sensitivity is only moderate. For staging recurrent disease, sensitivity depends on the level of serum PSA (PSA should be2 ng/ml). This applies to both choline and acetate. However, despite these limitations, a significant number of patients with recurrent disease can benefit from PET imaging by a change in treatment planning.