A summary of both clinical studies is provided in table 1.
Patient characteristics
Per protocol, all 20 patients had had adequate kidney function at baseline (see table 2). The kidney uptake on baseline 68Ga-PSMA-11 PET was also comparable between the two populations. The SGC patients had a significantly higher tumor burden than the low-volume mHSPC patients (p=<0.001). Figure 1 illustrates the baseline disease burden of 4 patients (2 mHSPC and 2 SGC). Furthermore, other baseline patient characteristics are presented in table 2.
Kidney absorbed radiation doses
Median kidney absorbed dose was 0.49 Gy/GBq (range: 0.34-0.66) for treatment with [177Lu]Lu‑PSMA-617, whereas the median kidney absorbed dose was 0.73 Gy/GBq (range: 0.42-1.31) for [177Lu]Lu-PSMA-I&T (table 3). The difference in absorbed dose between [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T was statistically significant (p=0.004). As depicted in figure 2, apart from the initial higher kidney activity at the earliest time-points with [177Lu]Lu-PSMA-I&T, both [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T show comparable kinetics over time. The median clearance half-lives were 26h (range: 15-43h) and 20h (range: 17-38h), for PSMA-617 and PSMA I&T, respectively (p=0.27).
Table 1: 177Lu-PSMA treatment and dosimetry imaging
|
mHSPC (n=10)
|
SGC (n=10)
|
PSMA ligand for PSMA-RLT
|
PSMA-617
|
PSMA-I&T
|
177Lu-PSMA-RLT treatment
|
cycle 1: 3 GBq
cycle 2: 6 GBq
|
2-4 cycles of 7.4 GBq
|
Dosimetry imaging
|
After cycle 1 + cycle 2
|
After
cycle 1
|
Cumulative activity*
|
9 GBq
|
7.4 GBq
|
Dosimetry imaging timepoints (post-injection)†
|
1h
24h
48h
72h
168h
|
1h
24h
48h
72h
168h
|
Clinical study
|
NCT03828838
|
NCT04291300
|
Abbreviations: mHSPC: low-volume metastatic hormone-sensitive prostate cancer patients, SGC: salivary gland cancer patients, PSMA: prostate-specific membrane antigen, RLT: radioligand therapy, 177Lu: lutetium-177, GBq: Giga-becquerel
*Total amount of activity for which dosimetry imaging data is available
†This included SPECT/CT imaging of the kidneys
Table 2: Baseline patient characteristics
|
mHSPC (n=10)
No. of pts (%)
|
SGC (n=10)
No. of pts (%)
|
p-value
|
Gender
Male
Female
|
10 (100)
0 (0)
|
5 (50)
5 (50)
|
0.033
|
Age, median (range)
|
67 (61-77)
|
64 (51-74)
|
0.272
|
Disease burden
≤10 tumor lesions >10 tumor lesions
|
10 (100)
0 (0)
|
1 (10)
9 (90)
|
<0.001
|
Kidney function*
eGFR† (mL/min), median (range)
|
71 (61-88)
|
90 (61-90)
|
0.005
|
Kidney uptake 68Ga-PSMA-11 PET*‡
SUVmax, median (range) SUVmean, median (range)
|
60.5 (35.7-97.4)
32.2 (16.9-51.2)
|
59.4 (23.5-72.9) 31.0 (12.1-40.0)
|
0.496
0.734
|
Median kidney VOI volume (mL) on SPECT/CT (range)
|
190 (130-250)
|
198 (160-295)
|
0.427
|
Abbreviations: mHSPC: low-volume metastatic hormone-sensitive prostate cancer patients, SGC: salivary gland cancer patients, eGFR: estimated glomerular filtration rate, 68Ga: Gallium-68, PSMA: prostate-specific membrane antigen, PET: positron emission tomography, SUVmax: maximum standardized uptake value, SUVmean: mean standardized uptake value, VOI: volume of interest.
*Maximum time-interval between baseline kidney function assessment and baseline 68Ga-PSMA-11 PET with the start of 177Lu-PSMA RLT was 4 weeks.
†eGFR: based on the CKD-EPI equation.
‡Time interval between 68Ga-PSMA injection and imaging was ±1 hour. 68Ga-PSMA dose was 2.0 MBq/kg ± 10%, with a minimum of 20 Mbq and a maximum of 300 Mbq.
Table 3: Kidney absorbed doses per injected activity of [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T
Kidney absorbed dose (Gy/GBq)
|
mHSPC (n=10)
[177Lu]Lu-PSMA-617
|
SGC (n=10)
[177Lu]Lu-PSMA-I&T
|
Median
|
0.49
|
0.73
|
Range
|
0.34 – 0.66
|
0.42 – 1.31
|
Abbreviations: mHSPC: low-volume metastatic hormone-sensitive prostate cancer patients, SGC: salivary gland cancer patients