SNMMI 2023: Tumour-to-Kidney Ratio on Pre-Therapeutic PSMA-PET-CT May Be Predictive of the Response [Of Lymphatic and Bone Metastases] to Therapy in mCRPC

(UroToday.com) The 2023 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting held in Chicago, IL between June 24^th and 27^th, 2023 was host to a prostate cancer session. Melanie Hohberg presented the results of an analysis evaluating whether tumor-to-kidney ratio on pre-treatment PSMA-PET/CT was predictive of treatment response in metastatic castrate-resistant prostate cancer (mCRPC) patients.

¹⁷⁷Lu-PSMA is currently approved for the treatment of mCRPC patients with disease progression following use of prior taxane-based chemotherapy and androgen receptor signaling inhibitors (ARSIs).^1,2 The objective of this study was to evaluate the absorbed dose of ¹⁷⁷Lu-PSMA in osseous and lymphatic metastases in mCRPC patients, and whether the mean dose changed over treatment cycles, stratified by treatment response status. Pre-treatment PSMA-PET/CTs were also evaluated for their ability to predict treatment response.

The investigators performed a retrospective analysis of 30 patients with mCRPC who received ≥3 cycles of ¹⁷⁷Lu-PSMA therapy (¹⁷⁷Lu-PSMA-I&T). Pre-treatment PET/CT scan were performed using either of the following two radiotracers: ¹⁸F-JK-PSMA-7 or ⁶⁸Ga-PSMA-HBED-CC. For each therapy cycle, the mean activity of ¹⁷⁷Lu-PSMA-I&T was 7,209 MBq +/- 379 MBq. Quantitative SPECT/CT images were obtained 24, 48, and 168 hours after ¹⁷⁷Lu-PSMA-I&T administration. Artificial intelligence-based segmentation of the kidneys and gradient-based segmentation of the lymph node and bone lesions were performed on pre-treatment PET/CT and the 1^st SPECT/CT images. Radiation dosimetry was performed using the MIM dosimetry software. Partial volume correction was also applied for all segmented volumes of interest. The tumor-to-kidney uptake ratio was quantified using the SUVmax, SUVpeak, SUVmean, and SUVmedian.

Response assessment was performed based on PSA levels:

Responders: PSA decline of ≥50%
Non-responder: Unchanged or increasing PSA level

Baseline PSA level was determined on the day of or the day prior to ¹⁷⁷Lu-PSMA-I&T initiation. The last PSA level assessed was six weeks following completion of the third therapy cycle.

Results from the kidney dosimetry are demonstrated below. There were no significant differences in renal mean dose (Gy/GBq) at the time of the 1^st, 2^nd, or 3^rd treatment cycle.

177Lu-PSMA-I&T kidney dosimetry
Next, the investigators evaluated mean doses among lymph node metastatic lesions among responders and non-responders. As seen below, responders had a 27% decrease in the mean dose between the 1^st and 2^nd cycles only, with no significant changes from the 2^nd to 3^rd cycle. Conversely, in non-responders, the mean dose in the lymph node lesions remained relatively stable throughout.
177Lu-PSMA-I&T lymph node
Among bone lesions, significant declines in mean dose among responders were observed from the 1^st to 2^nd (-33%) and 2^nd to 3^rd cycles (-50%). No significant differences in the mean doses of bone lesions were observed between the treatment cycles among non-responders.

bone lesions 177Lu-PSMA-I&T

Results of the residence time analysis mirrored those of the mean dose changes between treatment cycles among both responders and non-responders.

177Lu-PSMA-I&T residence time

Given that the mean kidney uptake was similar among responders and non-responders, the kidney uptake was used as the reference standard among the patient cohort. As seen in the PSMA-PET/CT images below, patient 1 had a significantly higher lesion/kidney uptake ratio (>1) and was a treatment responder. Conversely, patient 2 had an uptake ratio <1 and was a non-responder.

tumor to kidney ratio

The lymph node to kidneys uptake ratio among responders was consistently two-fold higher among treatment responders, irrespective of whether SUVpeak, SUVmean, SUVmedian, or SUVmax were evaluated.

177Lu-PSMA-I&T lymph node to kidney ratio table

A similar pattern was seen for bone lesion to kidneys uptake ratio among responders, with an uptake ratio of approximately two-fold higher, compared to non-responders.

177Lu-PSMA-I&T bone lesion to kidney ratio results

The authors concluded that:

Responders to ¹⁷⁷Lu-PSMA therapy, based on PSA criteria, achieved higher absorbed doses compared to non-responders
Absorbed doses decreased over the three therapy cycles among responders
Tumor-to-kidney uptake may serve as a parameter to identify potential responders on pre-treatment PSMA-PET/CT

Presented by: Melanie Hohberg, Research Scientist, MPE at Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany

Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, Chicago, IL, Sat, June 24 – Tues, June 27, 2023.

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