Clinical Translation of Targeted α-Therapy: An Evolution or a Revolution?

Benedikt Feuerecker; Clemens Kratochwil; Hojjat Ahmadzadehfar; Alfred Morgenstern; Matthias Eiber; Ken Herrmann; Kelsey L. Pomykala

doi:10.2967/jnumed.122.265353

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FIGURE 1.
Comparison of radiobiologic effects of ²²⁵Ac-PSMA and ¹⁷⁷Lu-PSMA. LET = linear energy transfer.
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FIGURE 2.
Patient with G2 (Ki-67, 5%) NET of right (resected) kidney received 3 cycles of 19 MBq of ²²⁵Ac-DOTATOC. Maximum-intensity projections of ⁶⁸Ga-DOTATOC PET/CT done in advance, between cycles, and after last cycle demonstrate antitumor activity (left). Despite remaining solitary left kidney, cumulative 47 MBq of ²²⁵Ac-DOTATOC did not lead to increase in serum creatinine (right, bottom) or estimated glomerular filtration rate (right, top) during 3 y of follow-up. eGFR = estimated glomerular filtration rate.
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FIGURE 3.
Initial promising results from Heidelberg group for patient with diffuse red bone marrow infiltration of mCRPC, which was considered contraindication for treatment with β-emitters. ⁶⁸Ga-PSMA-11 PET/CT scans demonstrating pretherapeutic tumor spread (A), restaging 2 mo after third cycle of ²²⁵Ac-PSMA-617 (B), and restaging 2 mo after 1 additional consolidation therapy (C). (Reprinted from (27).)

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TABLE 1.

Overview of Current Data on Compassionate Use of ²²⁵Ac-PSMA-617 RLT in Different Patient Cohorts: Effects of Treatment on PSA, Complete Remission in PET, and Median OS Are Summarized (34)

Cohort	Pretoria I	Pretoria II	Heidelberg	New Delhi	TUM	LMU	Pretoria III
	Chemo-naïve mHSPC/mCRPC	Early mCRPC	Intermediate mCRPC (7/40 after LuPSMA)	Early to intermediate	Late mCRPC (all after LuPSMA)	Early to intermediate mCRPC	mCRPC directly after ADT
n	17	73	40	28	26	18 (4 excluded because of incomplete follow-up)	53
	²²⁵Ac-PSMA-617	²²⁵Ac-PSMA-617	²²⁵Ac-PSMA-617	²²⁵Ac-PSMA-617	²²⁵Ac-PSMA-617	²²⁵Ac-PSMA-I&T	²²⁵Ac-PSMA-617
Prior mCRPC lines	(no CTx, no second ADT, 3× LuPSMA)	1–2	Median, 3 (range, 1–7)	(15 prior LuPSMA, 13 no LuPSMA)	Median, 6 (range, 3–8) (all after LuPSMA)	Median, 3 (range, 2–4) 11/14 after LuPSMA	1 (ADT)
Any PSA ↓	94% (16/17)	83% (60/73)	93% (37/40)	79% (22/28)	88% (23/26)	79% (11/14)	96% (51/53)
Max. ≥50% PSA ↓	88% (15/17)	70% (51/73)	75% (30/40)	39% (11/28)	65% (17/26)	50% (7/14)	91% (48/53)
Max. ≥90% PSA ↓	82% (14/17)	58%^* (42/73)	40%^* (16/40)	14% (4/28)^*	12% (3/26)	7% (1/14)^*	NA
CR on PET	65% (11/17)	29% (21/73)	NA	2/22 (9%)	0%	NA	56% (30/54)
Median cPFS	NA	15.2 mo (est.)	7 mo	12 mo	4.1 mo	NA	22 mo^†; 4 mo^‡
Median OS	NA	18 mo (est.)	>12 mo	17 mo	7.7 mo	NA	NA^†; 9 mo^‡
Publication	(32)	(33)	(31)	(35)	(34)	(28)	(61)

↵* Extracted from waterfall plot.
↵† Patients with PSA decline ≥ 50%.
↵‡ Patients with PSA decline < 50%.
TUM = Technische Universität München; LMU = Ludwig-Maximilians-Universität München; mHSPC = metastatic hormone-sensitive prostate cancer; ADT = androgen deprivation therapy; CTx = chemotherapy; max = maximum; NA = not available; CR = complete remission; est. = estimated.