First in-man study of <sup>68</sup>Ga-THP-PSMA PET in patients with primary prostate cancer: initial results — ASN Events
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First in-man study of 68Ga-THP-PSMA PET in patients with primary prostate cancer: initial results (#32)

Michael S Hofman 1 , Peter Eu 1 , Catherine Mitchell 1 , Phil Blower 2 , Amir Iravani 1 , Declan Murphy 1 , Jennifer Young 2 , Rod J Hicks 1 , Gregory E Mullen 2 3
  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom
  3. Theragnostics Ltd, London, United Kingdon

Ga-68 labelled urea-based inhibitors of the prostate specific membrane antigen (PSMA), such as 68Ga-HBED-PSMA-11, are promising peptides for targeting prostate cancer. The tris(hydroxypyridinone) (THP) ligand rapidly complexes 68Ga3+ at room temperature, at very low concentration and over a wide pH range, making it possible for the direct elution from a 68Ge/68Ga generator into a cold radiopharmaceutical kit  in one step without any manipulation. This first in-man study aimed to assess the safety and biodistribution of 68Ga-THP-PSMA (ACTRN: 12615001324505).

Methods: 8 patients with pathologically proven prostate cancer scheduled to undergo prostatectomy were recruited (mean age 61, range 46-71; Gleason score 7-10; PSA mean 7.8, range 5.4-10.6). 68Ga-THP-PSMA was administered with whole body PET/CT imaging performed at multiple time-points from administration to 180 minutes. Patients were followed-up for 24 hours to evaluate for adverse events. All patients proceeded to prostatectomy with PSMA immunohistochemistry performed. 7 patients also underwent pelvic nodal dissection.

Results: No adverse events occurred. Six of 8 patients had increased uptake in the prostate above background (at 2 h imaging: average SUVmax 5.1, range 2.4 – 9.2; volume 4.1 mL, range 1.4 - 10.4). Physiologic activity was seen in salivary glands, liver, spleen and duodenum; activity in these organs was significantly lower than our experienced with 68Ga-HBED-PSMA11, although direct comparison was not performed.  3+ immunohistochemistry staining was seen in 6 THP-PSMA positive scans, and 1+ / 2+ staining in the 2 THP-PSMA negative scans. Patients with SUVmax over 5 all had 3+ >80% PSMA staining. Pathologic pelvic nodal involvement was identified in 2 patients although <1mm in size and therefore not visualised on PET. One patient had focal uptake in sub-cm pelvic nodes without pathologic abnormality; follow-up is awaited to see if this represented sampling error.

Conclusion: 68Ga-THP-PSMA is safe. Focal uptake in prostate adenocarcinoma correlates with high PSMA expression.